surA

UniProt ID: P0ABZ6
Organism: Escherichia coli (strain K12)
Review Status: COMPLETE
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Gene Description

SurA is a periplasmic chaperone that functions as the primary pathway for delivery of unfolded outer membrane proteins (OMPs) to the BAM complex for insertion into the outer membrane. It also possesses peptidyl-prolyl cis-trans isomerase (PPIase) activity via its second parvulin domain, but this enzymatic activity is dispensable for its in vivo chaperone function. The N-terminal domain and C-terminal tail are necessary and sufficient for chaperone activity and OMP substrate recognition. SurA binds preferentially to unfolded OMPs, recognizing aromatic-rich peptide motifs characteristic of integral outer membrane beta-barrel proteins. It functions as a holdase, stabilizing unfolded OMPs in a dynamic state to prevent aggregation while enabling stepwise membrane insertion of beta-hairpins. SurA is required for the efficient folding of OmpA, OmpF, LamB, and FimD, and for overall outer membrane integrity. Loss of SurA leads to decreased outer membrane density and activates the sigmaE stress response.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0006457 protein folding
IBA
GO_REF:0000033
ACCEPT
Summary: SurA participates in the maturation of outer membrane porins, which involves conversion of unfolded monomers into folded monomers and subsequent trimerization (PMID:8985185). SurA mutants show defective folding of OmpA, OmpF, and LamB (PMID:8626309). The IBA annotation to protein folding is phylogenetically supported and consistent with experimental evidence.
Reason: SurA is directly involved in protein folding as demonstrated by multiple experimental studies. Loss of SurA blocks the LamB assembly pathway at a step prior to folded monomer formation (PMID:8985185), and surA mutants show defective folding of three outer membrane proteins (PMID:8626309). This IBA annotation is well supported.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN005352065 Β· PANTHER:PTN005352065 SUPPORTS TRANSFER
Current PTHR47637 PAINT retains protein folding at this node, seeded by P0ABZ6's own experimental evidence; target self-seeding is valid experimental grounding, not circular propagation.
Supporting Evidence:
PMID:8985185
We demonstrate that SurA is involved in the conversion of unfolded monomers into a newly identified intermediate in LamB assembly, which behaves as a folded monomer.
PMID:8626309
We determined that the efficient folding of three outer membrane proteins (OmpA, OmpF, and LamB) requires SurA in vivo
GO:0003755 peptidyl-prolyl cis-trans isomerase activity
IBA
GO_REF:0000033
ACCEPT
Summary: SurA has confirmed PPIase activity (EC 5.2.1.8) residing in its second parvulin domain (PMID:8985185, PMID:11226178). However, this enzymatic activity is dispensable for SurA's primary chaperone function in vivo, as a SurA variant lacking both parvulin domains is almost completely functional (PMID:11226178). The IBA annotation is phylogenetically supported and experimentally validated.
Reason: PPIase activity is experimentally confirmed for SurA (PMID:8985185) and is a real enzymatic activity of this protein, even though it is not essential for SurA's primary in vivo function. The IBA annotation is appropriate.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN005352065 Β· PANTHER:PTN005352065 SUPPORTS TRANSFER
Current PTHR47637 PAINT retains PPIase activity at this node, seeded by P0ABZ6's direct activity evidence; target self-seeding is expected and not circular.
Supporting Evidence:
PMID:8985185
SurA, a periplasmic protein with peptidyl-prolyl isomerase activity, participates in the assembly of outer membrane porins.
PMID:11226178
a variant of SurA lacking both parvulin-like domains exhibits a PPIase-independent chaperone-like activity in vitro and almost completely complements the in vivo function of intact SurA
GO:0030288 outer membrane-bounded periplasmic space
IBA
GO_REF:0000033
ACCEPT
Summary: SurA is a periplasmic protein with a cleavable signal peptide (residues 1-20). Multiple proteomics studies have confirmed its periplasmic localization (PMID:15911532, PMID:24140104, PMID:8985185). UniProt annotates it as periplasmic with the note that it can associate with the outer membrane.
Reason: Periplasmic localization is firmly established by direct experimental evidence (IDA from multiple studies) and is consistent with the IBA annotation.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN005352065 Β· PANTHER:PTN005352065 SUPPORTS TRANSFER
Current PTHR47637 PAINT retains this localization at the node, seeded by P0ABZ6's direct periplasmic-localization evidence.
Supporting Evidence:
PMID:8985185
SurA, a periplasmic protein with peptidyl-prolyl isomerase activity
GO:0051082 unfolded protein binding
IBA
GO_REF:0000033
MODIFY
Summary: SurA directly binds unfolded outer membrane proteins in the periplasm. Behrens et al. (PMID:11226178) demonstrated that SurA interacts preferentially (>50-fold) with in vitro synthesized porins over other similarly sized proteins, and this chaperone activity resides in the N-terminal and C-terminal domains independent of PPIase activity. Thoma et al. (PMID:26344570) characterized SurA as a holdase that stabilizes a dynamic unfolded state, preventing misfolding and allowing stepwise beta-hairpin insertion into the membrane. Per the UPB project decision rules, SurA functions as a holdase-type chaperone that prevents aggregation of unfolded OMPs in transit to the BAM complex. It does not actively refold substrates via ATPase cycles. Because SurA escorts an unfolded client to the defined YaeT/BAM acceptor, the carrier-specific GO:0140309 definition is satisfied even though movement occurs within one compartment.
Reason: GO:0051082 is now formally obsolete. SurA is described as a holdase chaperone by Thoma et al. (PMID:26344570), who explicitly titled their paper "Impact of holdase chaperones Skp and SurA on the folding of beta-barrel outer-membrane proteins." SurA stabilizes unfolded OMPs in a dynamic state without actively refolding them via ATPase cycles, instead allowing stepwise membrane insertion. SurA also escorts OMPs across the periplasm to the YaeT/BAM acceptor. The definition of GO:0140309 requires an acceptor molecule or a specific location, not movement through multiple compartments; BAM/YaeT satisfies that endpoint. GO:0140309 therefore captures the directly demonstrated carrier-holdase mechanism, whereas GO:0044183 is less specific and GO:0051082 is obsolete.
Propagation Review
Root cause: SOURCE STALE OR MISSING
Sources checked:
PANTHER:PTN005352065 Β· PANTHER:PTN005352065 SOURCE STALE OR MISSING
GOA still carries the obsolete GO:0051082 IBA from this node, but current PTHR47637 PAINT contains no GO:0051082 IBD row. The replacement is grounded independently in direct SurA experiments.
Supporting Evidence:
PMID:26344570
Either chaperone prevents FhuA from misfolding by stabilizing a dynamic, unfolded state, thus allowing the substrate to search for structural intermediates.
PMID:11226178
SurA interacts preferentially (>50-fold) with in vitro synthesized porins over other similarly sized proteins, leading us to suggest that the chaperone-like function of SurA preferentially facilitates maturation of outer membrane proteins.
PMID:17908933
SurA is the primary chaperone responsible for the periplasmic transit of the bulk mass of OMPs to the YaeT complex.
GO:0003755 peptidyl-prolyl cis-trans isomerase activity
IEA
GO_REF:0000120
ACCEPT
Summary: IEA annotation from InterPro/UniRule based on SurA's parvulin PPIase domains (IPR000297, IPR023034) and EC:5.2.1.8. This is consistent with experimental evidence (PMID:8985185) confirming PPIase activity.
Reason: The IEA annotation correctly reflects SurA's PPIase activity, which is experimentally confirmed. The annotation is broader than necessary (the PPIase activity resides only in the second parvulin domain) but the term itself is appropriate.
Supporting Evidence:
PMID:8985185
SurA, a periplasmic protein with peptidyl-prolyl isomerase activity
GO:0006457 protein folding
IEA
GO_REF:0000120
ACCEPT
Summary: IEA annotation from InterPro/UniRule. SurA's involvement in protein folding is well established experimentally (PMID:8985185, PMID:8626309).
Reason: Consistent with experimental evidence and IBA annotation. The IEA mapping correctly identifies SurA's role in protein folding.
Supporting Evidence:
PMID:8626309
SurA assists the folding of Escherichia coli outer membrane proteins.
GO:0016853 isomerase activity
IEA
GO_REF:0000043
KEEP AS NON CORE
Summary: IEA annotation from UniProtKB-KW (KW-0413 Isomerase). SurA is classified as an isomerase based on its PPIase activity (EC 5.2.1.8). This is a parent term of GO:0003755 (peptidyl-prolyl cis-trans isomerase activity), which is the more specific and informative term.
Reason: This very broad parent term is true but non-core because the experimentally supported child GO:0003755 identifies the actual isomerase activity.
Supporting Evidence:
PMID:8985185
SurA, a periplasmic protein with peptidyl-prolyl isomerase activity
GO:0030288 outer membrane-bounded periplasmic space
IEA
GO_REF:0000002
ACCEPT
Summary: IEA annotation from InterPro (IPR023034). Consistent with experimentally confirmed periplasmic localization (PMID:8985185, PMID:15911532, PMID:24140104).
Reason: The InterPro-derived localization is correct and supported by multiple experimental studies. Redundant with IDA and IBA annotations but acceptable.
Supporting Evidence:
PMID:8985185
SurA, a periplasmic protein with peptidyl-prolyl isomerase activity
GO:0042277 peptide binding
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: IEA annotation from InterPro (IPR023034). SurA does bind peptide motifs characteristic of OMPs, specifically recognizing aromatic-rich patterns. Bitto and McKay (PMID:14506253) showed that SurA binds peptide motifs found in integral outer membrane proteins. Hennecke et al. (PMID:15840585) demonstrated selective substrate recognition through features characteristic of OMPs.
Reason: SurA does bind OMP peptide motifs, so the annotation is retained. It is non-core because the carrier-holdase and PPIase terms convey the functional mechanisms more informatively.
Supporting Evidence:
PMID:11226178
SurA interacts preferentially (>50-fold) with in vitro synthesized porins over other similarly sized proteins
GO:0042597 periplasmic space
IEA
GO_REF:0000120
KEEP AS NON CORE
Summary: IEA annotation from UniProtKB-SubCell (SL-0200). SurA is located in the periplasmic space. This is a broader parent of GO:0030288 (outer membrane-bounded periplasmic space), which is also annotated. Both are correct.
Reason: Correct localization, retained as non-core because it is a broader parent of GO:0030288, which is independently supported by direct evidence.
Supporting Evidence:
PMID:8985185
SurA, a periplasmic protein with peptidyl-prolyl isomerase activity
GO:0043165 Gram-negative-bacterium-type cell outer membrane assembly
IEA
GO_REF:0000002
ACCEPT
Summary: IEA annotation from InterPro (IPR023034). SurA is critically involved in outer membrane assembly as the primary chaperone for OMP biogenesis (PMID:17908933, PMID:8985185).
Reason: Consistent with experimental evidence. SurA depletion causes marked decrease in outer membrane density (PMID:17908933), confirming its essential role in outer membrane assembly.
Supporting Evidence:
PMID:17908933
Depletion of SurA alone results in a marked decrease in outer membrane density
GO:0050821 protein stabilization
IEA
GO_REF:0000002
ACCEPT
Summary: IEA annotation from InterPro (IPR023034). SurA stabilizes unfolded OMPs in the periplasm, preventing their aggregation and degradation (PMID:8626309, PMID:26344570).
Reason: Consistent with direct IMP evidence that SurA stabilizes OMP clients. The IEA and experimental rows therefore receive the same core action.
Supporting Evidence:
PMID:26344570
Either chaperone prevents FhuA from misfolding by stabilizing a dynamic, unfolded state
GO:0051082 unfolded protein binding
IEA
GO_REF:0000120
MODIFY
Summary: IEA annotation from InterPro/UniRule. SurA binds unfolded OMPs as demonstrated experimentally (PMID:11226178). This term is now formally obsolete per the UPB project; see review of the IBA annotation for this term above.
Reason: Same rationale as the IBA GO:0051082 annotation above. SurA functions as a holdase chaperone for unfolded OMPs. GO:0051082 is now formally obsolete. Replace with GO:0140309 because SurA both stabilizes an unfolded OMP and escorts it to the YaeT/BAM acceptor; the carrier definition is satisfied.
Supporting Evidence:
PMID:11226178
SurA interacts preferentially (>50-fold) with in vitro synthesized porins over other similarly sized proteins
GO:0005515 protein binding
IPI
PMID:18165306
Analysis of YfgL and YaeT interactions through bioinformatic...
KEEP AS NON CORE
Summary: IntAct-derived annotation showing SurA interacts with BamB (YfgL, P77774). Vuong et al. (PMID:18165306) used genetic and biochemical approaches to show that SurA binds to BamA/YaeT or another BAM complex member without going through BamB/YfgL. The interaction with BamB itself is detected by IntAct but the paper primarily discusses YfgL-YaeT interactions and shows SurA-YaeT binding is independent of YfgL.
Reason: IPI asserts an observed interaction with BamB and there is no contradictory evidence, so the row is retained. Generic protein binding does not express SurA's carrier-holdase mechanism and is therefore non-core.
Supporting Evidence:
PMID:18165306
SurA binds to YaeT (or another complex member) without going through YfgL.
GO:0005515 protein binding
IPI
PMID:22544271
Genetic, biochemical, and molecular characterization of the ...
KEEP AS NON CORE
Summary: IntAct-derived annotation showing SurA interacts with BamB (P77774). Workman et al. (PMID:22544271) studied BamA POTRA domain mutations and showed that BamA-SurA interactions correlated with improved OMP biogenesis. The SurA-BamB interaction is detected but the paper focuses on BamA structure-function.
Reason: IPI asserts an observed BamB interaction and no evidence contradicts it. The generic term is retained as non-core because it does not identify SurA's carrier-holdase mechanism.
Supporting Evidence:
PMID:22544271
OMP biogenesis improved dramatically, and this correlated with improved BamA folding, BamA-SurA interactions, and LptD (lipopolysaccharide transporter) biogenesis.
GO:0006457 protein folding
IMP
PMID:8626309
SurA assists the folding of Escherichia coli outer membrane ...
ACCEPT
Summary: Lazar and Kolter (PMID:8626309) used trypsin sensitivity as a folding assay and demonstrated that the efficient folding of three outer membrane proteins (OmpA, OmpF, and LamB) requires SurA in vivo, while folding of four periplasmic proteins was independent of SurA.
Reason: Strong experimental evidence (IMP) directly demonstrating SurA's role in protein folding. The trypsin sensitivity assay is a validated approach for assessing protein conformation, and the specificity for OMPs over periplasmic proteins is informative.
Supporting Evidence:
PMID:8626309
We determined that the efficient folding of three outer membrane proteins (OmpA, OmpF, and LamB) requires SurA in vivo, while the folding of four periplasmic proteins was independent of SurA.
GO:0006457 protein folding
IMP
PMID:8985185
SurA, a periplasmic protein with peptidyl-prolyl isomerase a...
ACCEPT
Summary: Rouviere and Gross (PMID:8985185) demonstrated that SurA is involved in the conversion of unfolded LamB monomers into folded monomers. Absence of SurA blocks the assembly pathway and leads to accumulation of species prior to the folded monomer stage.
Reason: Strong experimental evidence (IMP) showing SurA is required for protein folding of LamB. The identification of a specific folding intermediate (folded monomer) that requires SurA provides direct evidence for involvement in protein folding.
Supporting Evidence:
PMID:8985185
We demonstrate that SurA is involved in the conversion of unfolded monomers into a newly identified intermediate in LamB assembly, which behaves as a folded monomer.
GO:0036506 maintenance of unfolded protein
IDA
PMID:26344570
Impact of holdase chaperones Skp and SurA on the folding of ...
ACCEPT
Summary: Thoma et al. (PMID:26344570) used single-molecule force spectroscopy and NMR to demonstrate that SurA (and Skp) function as holdase chaperones that stabilize a dynamic unfolded state of the OMP FhuA. SurA prevents misfolding by maintaining the polypeptide in an unfolded, folding-competent state that allows stepwise beta-hairpin insertion.
Reason: This is a core function of SurA. The term "maintenance of unfolded protein" (GO:0036506) accurately describes SurA's holdase mechanism of keeping OMPs in a dynamic unfolded state until they can insert into the membrane. This is direct experimental evidence from single-molecule studies.
Supporting Evidence:
PMID:26344570
Either chaperone prevents FhuA from misfolding by stabilizing a dynamic, unfolded state, thus allowing the substrate to search for structural intermediates.
PMID:26344570
the SurA-chaperoned FhuA polypeptide inserts beta-hairpins into the membrane in a stepwise manner until the beta-barrel is folded
GO:0043165 Gram-negative-bacterium-type cell outer membrane assembly
IGI
PMID:17908933
Defining the roles of the periplasmic chaperones SurA, Skp, ...
ACCEPT
Summary: Sklar et al. (PMID:17908933) used depletion analysis and genetic interactions to establish that SurA is the primary chaperone for periplasmic transit of OMPs to the YaeT/BamA complex. SurA and YaeT interact directly in vivo. Depletion of SurA alone results in a marked decrease in outer membrane density. The IGI evidence reflects the genetic interaction analysis with Skp/DegP.
Reason: Strong genetic evidence demonstrating SurA's essential role in outer membrane assembly. The study establishes the SurA pathway as the primary route for OMP biogenesis, with Skp/DegP serving as a rescue pathway.
Supporting Evidence:
PMID:17908933
SurA is the primary chaperone responsible for the periplasmic transit of the bulk mass of OMPs to the YaeT complex.
PMID:17908933
Depletion of SurA alone results in a marked decrease in outer membrane density
GO:0043165 Gram-negative-bacterium-type cell outer membrane assembly
IMP
PMID:8985185
SurA, a periplasmic protein with peptidyl-prolyl isomerase a...
ACCEPT
Summary: Rouviere and Gross (PMID:8985185) demonstrated that SurA participates in the assembly of outer membrane porins. Loss of SurA blocks the LamB assembly pathway and leads to accumulation of unfolded intermediates.
Reason: Direct experimental evidence showing SurA is required for outer membrane protein assembly. This is a core function of SurA.
Supporting Evidence:
PMID:8985185
SurA, a periplasmic protein with peptidyl-prolyl isomerase activity, participates in the assembly of outer membrane porins.
GO:0050821 protein stabilization
IMP
PMID:8626309
SurA assists the folding of Escherichia coli outer membrane ...
ACCEPT
Summary: Lazar and Kolter (PMID:8626309) showed that SurA is required for maintaining the stability/conformation of outer membrane proteins. In surA mutants, OMPs become trypsin-sensitive, indicating loss of stable folded conformation.
Reason: The trypsin sensitivity assay demonstrates that SurA contributes to protein stabilization of OMPs. Loss of SurA leads to unstable OMP conformations. This is consistent with SurA's chaperone function.
Supporting Evidence:
PMID:8626309
We tested whether SurA was involved in folding periplasmic and outer membrane proteins by using trypsin sensitivity as an assay for protein conformation.
GO:0005515 protein binding
IPI
PMID:11226178
The SurA periplasmic PPIase lacking its parvulin domains fun...
KEEP AS NON CORE
Summary: Behrens et al. (PMID:11226178) demonstrated that SurA interacts preferentially with in vitro synthesized porins (including OmpF, P02932) over other similarly sized proteins. This interaction reflects SurA's chaperone substrate specificity.
Reason: IPI accurately records the experimentally observed OmpF interaction and no evidence contradicts it. It remains non-core because GO:0140309 and GO:0036506 convey the substrate-chaperoning mechanism rather than generic binding.
Supporting Evidence:
PMID:11226178
SurA interacts preferentially (>50-fold) with in vitro synthesized porins over other similarly sized proteins
GO:0005515 protein binding
IPI
PMID:17908933
Defining the roles of the periplasmic chaperones SurA, Skp, ...
KEEP AS NON CORE
Summary: Sklar et al. (PMID:17908933) demonstrated that SurA and YaeT (BamA, P0A940) interact directly in vivo. This interaction is functionally significant as SurA delivers OMPs to the YaeT/BAM complex for membrane insertion.
Reason: IPI accurately records the direct BamA/YaeT interaction and no evidence contradicts it. It is retained as non-core because the interaction is more informatively interpreted through GO:0140309 and outer-membrane assembly.
Supporting Evidence:
PMID:17908933
we demonstrate that SurA and YaeT interact directly in vivo
GO:0005515 protein binding
IPI
PMID:18165306
Analysis of YfgL and YaeT interactions through bioinformatic...
KEEP AS NON CORE
Summary: Vuong et al. (PMID:18165306) from EcoCyc annotation showing SurA binds to BamA/YaeT (P0A940). The paper demonstrates that SurA binds to YaeT or another BAM complex member independently of YfgL/BamB.
Reason: IPI accurately records a BamA/YaeT interaction and no evidence contradicts it. It is retained as non-core because generic binding is less informative than the carrier-holdase and outer-membrane-assembly annotations.
Supporting Evidence:
PMID:18165306
SurA binds to YaeT (or another complex member) without going through YfgL.
GO:0030288 outer membrane-bounded periplasmic space
IDA
PMID:15911532
Localization, annotation, and comparison of the Escherichia ...
ACCEPT
Summary: Lopez-Campistrous et al. (PMID:15911532) identified SurA in the periplasmic fraction through proteomic analysis using biochemical fractionation followed by 2D gel electrophoresis and tandem mass spectrometry.
Reason: Direct experimental evidence (IDA) from proteomics confirming periplasmic localization. Consistent with signal peptide cleavage and all other evidence.
Supporting Evidence:
PMID:15911532
2,160 were annotated and assigned to the cytosol, periplasm, inner membrane, and outer membrane by biochemical fractionation followed by two-dimensional gel electrophoresis and tandem mass spectrometry
GO:0030288 outer membrane-bounded periplasmic space
IDA
PMID:24140104
Comparison of the large-scale periplasmic proteomes of the E...
ACCEPT
Summary: Han et al. (PMID:24140104) identified SurA in the periplasmic proteome of E. coli K-12 using large-scale periplasmic fractionation and mass spectrometry.
Reason: Direct experimental evidence (IDA) from periplasmic proteomics confirming localization. Consistent with all other evidence for periplasmic localization.
Supporting Evidence:
PMID:24140104
high-resolution periplasmic proteome reference maps of the E. coli K-12 and B strains were constructed
GO:0050821 protein stabilization
IMP
PMID:21784935
The fimbrial usher FimD follows the SurA-BamB pathway for it...
ACCEPT
Summary: Palomino et al. (PMID:21784935) demonstrated that FimD protein levels are dramatically reduced (~30-fold) in a surA null mutant. Using a conditional surA mutant, they showed FimD is depleted from bacteria in parallel to SurA depletion, demonstrating SurA's direct role in stabilizing FimD.
Reason: Strong experimental evidence (IMP) showing SurA is required for the stability of FimD usher protein. The conditional depletion experiment provides direct evidence for SurA-dependent protein stabilization.
Supporting Evidence:
PMID:21784935
The FimD level is dramatically reduced (∼30-fold) in a surA null mutant
PMID:21784935
FimD is depleted from bacteria in parallel to SurA without significant upregulation of DegP
GO:0030288 outer membrane-bounded periplasmic space
IDA
PMID:8985185
SurA, a periplasmic protein with peptidyl-prolyl isomerase a...
ACCEPT
Summary: Rouviere and Gross (PMID:8985185) characterized SurA as a periplasmic protein in the original study identifying its role in OMP assembly.
Reason: Foundational experimental evidence for periplasmic localization from the key characterization study.
Supporting Evidence:
PMID:8985185
SurA, a periplasmic protein with peptidyl-prolyl isomerase activity
GO:0051082 unfolded protein binding
IPI
PMID:11226178
The SurA periplasmic PPIase lacking its parvulin domains fun...
MODIFY
Summary: Behrens et al. (PMID:11226178) showed that SurA exhibits chaperone activity and interacts preferentially with in vitro synthesized porins (OmpA/P02931, OmpF/P02932, LamB/P02943) with >50-fold selectivity over other proteins. The interaction is mediated by the N-terminal and C-terminal domains, independent of PPIase activity. This is direct evidence for SurA binding unfolded OMPs.
Reason: Same rationale as other GO:0051082 annotations. GO:0051082 is now formally obsolete. SurA's binding to unfolded porins is one component of its carrier-holdase activity, and independent experiments establish escort to YaeT/BAM. Replace with GO:0140309.
Supporting Evidence:
PMID:11226178
a variant of SurA lacking both parvulin-like domains exhibits a PPIase-independent chaperone-like activity in vitro and almost completely complements the in vivo function of intact SurA
PMID:11226178
SurA interacts preferentially (>50-fold) with in vitro synthesized porins over other similarly sized proteins
GO:0003755 peptidyl-prolyl cis-trans isomerase activity
IDA
PMID:8985185
SurA, a periplasmic protein with peptidyl-prolyl isomerase a...
ACCEPT
Summary: Rouviere and Gross (PMID:8985185) demonstrated that SurA has peptidyl-prolyl isomerase activity. The PPIase activity was confirmed biochemically and the EC number 5.2.1.8 was assigned. However, later work showed this activity is dispensable for SurA's primary function (PMID:11226178).
Reason: Direct experimental evidence (IDA) for PPIase enzymatic activity. Although this activity is dispensable for SurA's primary chaperone function in vivo, it is a real, experimentally demonstrated enzymatic activity of this protein.
Supporting Evidence:
PMID:8985185
SurA, a periplasmic protein with peptidyl-prolyl isomerase activity, participates in the assembly of outer membrane porins.
GO:0140309 unfolded protein holdase activity
IDA
PMID:26344570
Impact of holdase chaperones Skp and SurA on the folding of ...
NEW
Summary: Direct biophysical experiments show SurA stabilizing a dynamic unfolded FhuA state during stepwise membrane insertion, while depletion and interaction studies establish delivery of OMPs to YaeT/BAM. BAM is the defined acceptor molecule required by the carrier-specific GO:0140309 definition.
Reason: GO:0140309 is more specific than GO:0044183 for SurA's mechanism. It does not require movement between compartments: its definition requires escort to an acceptor molecule or specific location. SurA binds unfolded OMPs, prevents misfolding in transit, and hands them to YaeT/BAM for membrane insertion. PMID:26344570 supplies the IDA basis by directly demonstrating unfolded-state stabilization and stepwise insertion into the membrane; PMID:17908933 independently supplies the YaeT/BAM acceptor endpoint through depletion and interaction evidence. The obsolete GO:0051082 author claim is not retained.
Supporting Evidence:
PMID:26344570
Either chaperone prevents FhuA from misfolding by stabilizing a dynamic, unfolded state, thus allowing the substrate to search for structural intermediates.
PMID:17908933
SurA is the primary chaperone responsible for the periplasmic transit of the bulk mass of OMPs to the YaeT complex.
file:projects/UNFOLDED_PROTEIN_BINDING.md
to an acceptor molecule or to a specific location
file:ECOLI/surA/surA-deep-research-falcon.md
SurA protects newly translocated, unfolded OMPs from **aggregation** in the crowded, ATP-free periplasm and **delivers** them to the outer-membrane Ξ²-barrel assembly machinery (**BAM** complex) for folding and insertion

Core Functions

Carrier-holdase activity -- SurA functions as the primary periplasmic chaperone for outer membrane protein biogenesis. It binds unfolded OMPs via its N-terminal and C-terminal domains (independent of PPIase activity) and escorts them to the BAM complex. SurA acts as a holdase, stabilizing OMPs in a dynamic unfolded state to prevent off-pathway misfolding while enabling stepwise beta-hairpin membrane insertion.

Supporting Evidence:
  • PMID:11226178
    a variant of SurA lacking both parvulin-like domains exhibits a PPIase-independent chaperone-like activity in vitro and almost completely complements the in vivo function of intact SurA
  • PMID:17908933
    SurA is the primary chaperone responsible for the periplasmic transit of the bulk mass of OMPs to the YaeT complex.
  • PMID:26344570
    the SurA-chaperoned FhuA polypeptide inserts Ξ²-hairpins into the membrane in a stepwise manner until the Ξ²-barrel is folded
  • file:projects/UNFOLDED_PROTEIN_BINDING.md
    to an acceptor molecule or to a specific location
  • file:ECOLI/surA/surA-deep-research-falcon.md
    SurA protects newly translocated, unfolded OMPs from **aggregation** in the crowded, ATP-free periplasm and **delivers** them to the outer-membrane Ξ²-barrel assembly machinery (**BAM** complex) for folding and insertion

Peptidyl-prolyl cis-trans isomerase activity -- SurA has PPIase activity (EC 5.2.1.8) residing in its second parvulin domain. This is a real enzymatic activity but is dispensable for SurA's primary in vivo chaperone function.

Supporting Evidence:
  • PMID:8985185
    SurA, a periplasmic protein with peptidyl-prolyl isomerase activity, participates in the assembly of outer membrane porins.
  • PMID:11226178
    a variant of SurA lacking both parvulin-like domains exhibits a PPIase-independent chaperone-like activity in vitro and almost completely complements the in vivo function of intact SurA

References

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Deep Research

Falcon

(surA-deep-research-falcon.md)

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πŸ“š Additional Documentation

Notes

(surA-notes.md)

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Bioreason Rl Predictions

(surA-bioreason-rl-predictions.md)

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Bioreason Rl Review

(surA-bioreason-rl-review.md)

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