Gram-negative outer-membrane protein chaperone delivery

A periplasmic carrier-holdase module for Gram-negative beta-barrel outer-membrane protein biogenesis. SurA is the primary route for bulk OMP transit to the BAM/YaeT assembly complex, while the trimeric Skp chaperone provides a parallel ATP-independent holdase route that maintains OMP clients in soluble unfolded states and cooperates with lipopolysaccharide; DegP contributes an optional quality-control branch that can clear or, under some conditions, protect unfolded OMPs in protease-chaperone cages. Sec export across the inner membrane, BAM-mediated membrane insertion itself, and LPS synthesis are outside this focused module.

MODULE:gram_negative_omp_biogenesisDRAFTCONCRETEBiological Processmodules/gram_negative_omp_biogenesis.yaml

Gram-negative-bacterium-type cell outer membrane assemblyGO:0043165 unfolded protein holdase activityGO:0140309

GO:0043165

Gram-negative-bacterium-type cell outer membrane assembly

Defines the OMP assembly process served by periplasmic carrier-holdases.

GO:0140309

unfolded protein holdase activity

Defines the carrier-holdase activity of escorting unfolded clients to a defined acceptor molecule or location.

file:genes/ECOLI/surA/surA-ai-review.yaml

ECOLI surA gene review

The completed E. coli surA review grounds SurA as the primary periplasmic carrier-holdase that delivers unfolded OMPs to BAM/YaeT.

file:genes/ECOLI/Skp/Skp-ai-review.yaml

ECOLI Skp gene review

The completed E. coli Skp review grounds Skp as a trimeric periplasmic carrier-holdase for unfolded OMP clients.

file:genes/ECOLI/degP/degP-ai-review.yaml

ECOLI degP gene review

The completed E. coli degP review grounds DegP as a periplasmic serine endoprotease with a secondary, purified-protein chaperone mode.

PMID:11226178

The SurA periplasmic PPIase lacking its parvulin domains functions in vivo and has chaperone activity.

Establishes that SurA has a PPIase-independent chaperone activity sufficient for near-normal in vivo function.

PMID:17908933

Defining the roles of the periplasmic chaperones SurA, Skp, and DegP in Escherichia coli.

Places SurA on the primary periplasmic OMP transit route to YaeT/BAM and identifies the Skp/DegP system as a rescue route when SurA is absent.

PMID:26344570

Impact of holdase chaperones Skp and SurA on the folding of beta-barrel outer-membrane proteins.

Supports the holdase interpretation by showing how Skp and SurA influence beta-barrel OMP folding.

PMID:10455120

Skp, a molecular chaperone of gram-negative bacteria, is required for the formation of soluble periplasmic intermediates of outer membrane proteins.

Establishes that Skp generates and maintains soluble periplasmic OMP folding intermediates.

PMID:19181847

The cavity-chaperone Skp protects its substrate from aggregation but allows independent folding of substrate domains.

Supports the model that Skp binds beta-barrel substrates in an unfolded, aggregation-protected state during periplasmic transit.

PMID:15304217

Crystal structure of Skp, a prefoldin-like chaperone that protects soluble and membrane proteins from aggregation.

Establishes the trimeric Skp cavity architecture and ATP-independent chaperone mechanism.

PMID:12509434

Folding and insertion of the outer membrane protein OmpA is assisted by the chaperone Skp and by lipopolysaccharide.

Shows that lipopolysaccharide is required together with Skp for efficient OmpA folding into lipid bilayers.

PMID:17928002

The trimeric periplasmic chaperone Skp of Escherichia coli forms 1:1 complexes with outer membrane proteins via hydrophobic and electrostatic interactions.

Supports direct Skp binding to lipopolysaccharide during OMP folding.

PMID:24373465

DegP primarily functions as a protease for the biogenesis of β-barrel outer membrane proteins in the Gram-negative bacterium Escherichia coli.

Establishes unfolded OMPs as major native DegP substrates and DegP's dominant OMP-biogenesis role as proteolytic clearance.

PMID:10319814

A temperature-dependent switch from chaperone to protease in a widely conserved heat shock protein.

Establishes DegP's low-temperature chaperone mode in vitro.

SurA is the major OMP delivery route, Skp is kept as a parallel/rescue route rather than as an equal bulk-flux route, and DegP is represented as the Skp-associated rescue-clearance branch rather than as a primary BAM delivery carrier.

4Nodes

3Parts

0Variant Sets

0Variants

5Annotons

0Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:gram_negative_omp_biogenesis deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

5 gene-function check(s) reflected in core functions · 0 conflict(s) · 0 evidence or coverage gap(s) (5 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

Annoton	Participant	Function	Assessment
sura_carrier_holdase	E. coli SurA UniProtKB:P0ABZ6 Gene	unfolded protein holdase activity GO:0140309	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
skp_carrier_holdase	E. coli Skp UniProtKB:P0AEU7 Gene	unfolded protein holdase activity GO:0140309	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
skp_lps_binding	E. coli Skp UniProtKB:P0AEU7 Gene	lipopolysaccharide binding GO:0001530	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
degp_omp_serine_endopeptidase	E. coli DegP UniProtKB:P0C0V0 Gene	serine-type endopeptidase activity GO:0004252	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
degp_temperature_switched_chaperone	E. coli DegP UniProtKB:P0C0V0 Gene	protein folding chaperone GO:0044183	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).

Gene-review completeness (3/3 grounded genes reviewed)

2 complete review(s) · 2 with deep research · 0 missing review · 1 reviewed but lacking deep research

Gene	Review	Complete	Deep research
degP P0C0V0	✓	✓	✗
Skp P0AEU7	✓	33/34	✓
surA P0ABZ6	✓	✓	✓

Tree

Gram-negative outer-membrane protein chaperone deliveryBiological Processgram_negative_omp_biogenesis

Parts
1. 1. primary SurA-mediated OMP delivery to BAM
2. SurA-mediated OMP deliveryBiological Processsura_omp_delivery
  
  Annotons
  - SurA OMP carrier-holdase Gene Product: E. coli SurA
3. 2. parallel Skp OMP holdase route optional
4. Skp-assisted OMP deliveryBiological Processskp_omp_delivery
  
  Annotons
  - Skp OMP carrier-holdase Gene Product: E. coli Skp
  - Skp lipopolysaccharide binding Gene Product: E. coli Skp
5. 3. DegP OMP rescue and clearance optional
6. DegP OMP quality controlBiological Processdegp_omp_quality_control
  
  Annotons
  - DegP OMP protease Gene Product: E. coli DegP
  - DegP temperature-switched OMP chaperone Gene Product: E. coli DegP

Details

Context

bacteriaNCBITaxon:2

Gram-negative outer-membrane protein chaperone deliveryBiological Processgram_negative_omp_biogenesis

Gram-negative-bacterium-type cell outer membrane assemblyGO:0043165 unfolded protein holdase activityGO:0140309

Context

bacteriaNCBITaxon:2

Part 1: primary SurA-mediated OMP delivery to BAM

SurA-mediated OMP deliveryBiological Processsura_omp_delivery

Annotons

SurA OMP carrier-holdase

sura_carrier_holdase

Participant: Gene Product: E. coli SurA

Gene Product:

E. coli SurAUniProtKB:P0ABZ6

Function

unfolded protein holdase activityGO:0140309

Substrates: unfolded beta-barrel outer-membrane protein

Products: BAM-engaged beta-barrel outer-membrane protein

Processes

Gram-negative-bacterium-type cell outer membrane assemblyGO:0043165 protein foldingGO:0006457

Locations

outer membrane-bounded periplasmic spaceGO:0030288

Primary periplasmic carrier-holdase that keeps unfolded OMPs soluble and routes them to BAM/YaeT for outer-membrane insertion.

file:genes/ECOLI/surA/surA-ai-review.yaml

SurA is reviewed as a primary periplasmic OMP carrier-holdase.

PMID:11226178

SurA has a PPIase-independent chaperone activity sufficient for in vivo function.

PMID:17908933

SurA is the major periplasmic route for OMP transit to YaeT/BAM.

Part 2: parallel Skp OMP holdase route (optional)

Skp-assisted OMP deliveryBiological Processskp_omp_delivery

Annotons

Skp OMP carrier-holdase

skp_carrier_holdase

Participant: Gene Product: E. coli Skp

Gene Product:

E. coli SkpUniProtKB:P0AEU7

Function

unfolded protein holdase activityGO:0140309

Substrates: unfolded beta-barrel outer-membrane protein

Products: soluble unfolded beta-barrel OMP-Skp complex

Processes

protein foldingGO:0006457 Gram-negative-bacterium-type cell outer membrane assemblyGO:0043165

Locations

outer membrane-bounded periplasmic spaceGO:0030288

Trimeric periplasmic holdase that shelters unfolded OMPs in a central cavity and helps keep them assembly-competent.

file:genes/ECOLI/Skp/Skp-ai-review.yaml

Skp is reviewed as a trimeric periplasmic OMP carrier-holdase.

PMID:10455120

Skp generates and maintains soluble periplasmic OMP folding intermediates.

PMID:19181847

Skp protects OMP clients from aggregation while leaving substrate domains dynamic.

Skp lipopolysaccharide binding

skp_lps_binding

Participant: Gene Product: E. coli Skp

Gene Product:

E. coli SkpUniProtKB:P0AEU7

Function

lipopolysaccharide bindingGO:0001530

Substrates: lipopolysaccharide

Processes

Gram-negative-bacterium-type cell outer membrane assemblyGO:0043165

Locations

outer membrane-bounded periplasmic spaceGO:0030288

LPS binding contributes to efficient Skp-assisted OMP folding and insertion at the outer membrane.

file:genes/ECOLI/Skp/Skp-ai-review.yaml

Skp is reviewed as a lipopolysaccharide-binding OMP chaperone.

PMID:15304217

Skp has a putative LPS binding site and interacts directly with LPS.

PMID:12509434

LPS is required together with Skp for efficient OmpA folding into lipid bilayers.

PMID:17928002

Skp-LPS interactions contribute to productive OMP folding.

Part 3: DegP OMP rescue and clearance (optional)

DegP OMP quality controlBiological Processdegp_omp_quality_control

Annotons

DegP OMP protease

degp_omp_serine_endopeptidase

Participant: Gene Product: E. coli DegP

Gene Product:

E. coli DegPUniProtKB:P0C0V0

Function

serine-type endopeptidase activityGO:0004252

Substrates: unfolded beta-barrel outer-membrane protein

Products: OMP-derived peptides

Processes

protein quality control for misfolded or incompletely synthesized proteinsGO:0006515 proteolysisGO:0006508

Locations

outer membrane-bounded periplasmic spaceGO:0030288

PDZ-regulated HtrA-family serine protease that degrades unfolded OMPs in cage-like oligomers instead of delivering them to BAM.

file:genes/ECOLI/degP/degP-ai-review.yaml

DegP is reviewed as a periplasmic serine endoprotease.

PMID:24373465

DegP's dominant in vivo OMP-biogenesis role is proteolytic clearance.

DegP temperature-switched OMP chaperone

degp_temperature_switched_chaperone

Participant: Gene Product: E. coli DegP

Gene Product:

E. coli DegPUniProtKB:P0C0V0

Function

protein folding chaperoneGO:0044183

Substrates: non-native periplasmic protein

Processes

protein foldingGO:0006457 protein quality control for misfolded or incompletely synthesized proteinsGO:0006515

Locations

outer membrane-bounded periplasmic spaceGO:0030288

In vitro lower-temperature DegP mode that can protect non-native proteins as a chaperone rather than immediately degrading them.

file:genes/ECOLI/degP/degP-ai-review.yaml

DegP is reviewed as having a secondary in vitro chaperone activity.

PMID:10319814

Spiess et al. established DegP's low-temperature chaperone mode in vitro.

PMID:24373465

Ge et al. found little appreciable DegP chaperone activity in cells.