Gram-negative lipoprotein-peptidoglycan tether remodeling

A reusable Gram-negative bacterial module for reversible covalent attachment of an outer-membrane lipoprotein to peptidoglycan. An ErfK-family L,D-transpeptidase transfers a tetrapeptide-stem donor onto the C terminus of a Braun-lipoprotein-like substrate, and a YafK/LdtF-family cysteine hydrolase can release the lipoprotein by cleaving the resulting amide bond. These reactions remodel the connection between the outer membrane and sacculus; they do not represent peptidoglycan glycan polymerization or canonical 4-3 peptide crosslinking by penicillin-binding proteins.

MODULE:gram_negative_lipoprotein_peptidoglycan_tether_remodelingDRAFTBiological Processmodules/gram_negative_lipoprotein_peptidoglycan_tether_remodeling.yaml
peptidoglycan-protein cross-linkingGO:0018104
GO:0018104
peptidoglycan-protein cross-linking
Defines covalent attachment of a protein substrate to peptidoglycan.
PMID:37255442
Characterization of Pseudomonas aeruginosa l,d-Transpeptidases and Evaluation of Their Role in Peptidoglycan Adaptation to Biofilm Growth.
Experiments in Pseudomonas aeruginosa establish OprI anchoring by the PP_2320-related ErfK subfamily. The full-text discussion tentatively assigns tether hydrolysis to the PP_1451-related YafK subfamily from its lack of detectable amide-bond-forming activity and close similarity to E. coli YafK.
The function of LdtPae3 was tentatively assigned to the release of OprI based on both the absence of detectable amide bond-forming activity (formation of 3→3 and tripeptide→ OprI bonds) and the close similarity between LdtPae3 and E. coli hydrolase YafK.
PMID:33941679
Cleavage of Braun's lipoprotein Lpp from the bacterial peptidoglycan by a paralog of l,d-transpeptidases, LdtF.
Genetic and biochemical experiments identify E. coli LdtF/YafK as a murein endopeptidase that cleaves Lpp from peptidoglycan.
Here, using genetic and biochemical approaches, we show that LdtF (formerly yafK), a newly identified paralog of l,d-transpeptidases in E. coli, is a murein hydrolytic enzyme that catalyzes cleavage of Lpp from the PG sacculus.
PMID:33947763
DpaA Detaches Braun's Lipoprotein from Peptidoglycan.
Independent biochemical work identifies the same E. coli enzyme as DpaA and demonstrates hydrolysis of the Lpp-peptidoglycan linkage.
We now show that LdtF hydrolyzes the Lpp-peptidoglycan linkage, detaching Lpp from peptidoglycan, and have renamed LdtF to peptidoglycan meso-diaminopimelic acid protein amidase A (DpaA).
PMID:42100858
Outer Membrane-Peptidoglycan Anchoring in Pseudomonas aeruginosa.
PA2854/Q9HZZ0 directly anchors OprI to peptidoglycan in live P. aeruginosa, and the reaction was reconstituted with purified components.
We document that the gene product of PA2854 is the catalyst that performs this transformation between the cell wall and the outer-membrane lipoprotein OprI in live Pseudomonas aeruginosa.

The two PSEPK proteins are assigned by exact PANTHER subfamily correspondence to functionally distinguished Pseudomonas aeruginosa enzymes. The anchoring activity of the PP_2320-related enzyme was demonstrated directly, whereas hydrolysis by PA14 LdtPae3 was assigned tentatively and remains an orthology-based prediction for PP_1451. The PA14 experimental accessions are resolved by locus: PA14_27180 is A0A0H2ZCT9 and PA14_15840 is A0A0H2ZF55. The hydrolysis family is independently anchored by experimentally characterized E. coli DpaA/LdtF (P0AA99), which shares PTHR36699:SF1 with PP_1451. PP_2320 is near oprI in KT2440 with PP_2321 intervening; this proximity is corroborative context, not evidence for a defined operon. GO:0071972 is asserted only for tether formation; no GO molecular-function term currently names hydrolysis of the peptidoglycan-protein tether, so that leaf retains a precise free-text function without an invented ontology identifier. Covalent lipoprotein-peptidoglycan tethering is not universal among Gram-negative bacteria, and the exact lipoprotein acceptor chemistry can differ between the enterobacterial Lpp and pseudomonad OprI systems; the module therefore describes reaction roles without imposing the E. coli Lpp C-terminal-lysine mechanism on every taxon.

3Nodes
2Parts
0Variant Sets
0Variants
2Annotons
1Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • gram_negative_lipoprotein_peptidoglycan_tether_remodeling-deep-research-openscientist.md (openscientist)

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (2/7 grounded genes reviewed)

2 complete review(s) · 1 with deep research · 5 missing review · 1 reviewed but lacking deep research

Gene Review Complete Deep research
Pseudomonas aeruginosa PA14 LdtPae2 A0A0H2ZCT9 ✗ — —
Pseudomonas aeruginosa PA14 LdtPae3 candidate A0A0H2ZF55 ✗ — —
Escherichia coli DpaA/LdtF experimental exemplar P0AA99 ✗ — —
PP_1451 Q88MW7 ✓ ✓ ✗
PP_2320 Q88KH0 ✓ ✓ ✓
Braun-lipoprotein-like outer-membrane lipoprotein Q88KG8 ✗ — —
Pseudomonas aeruginosa PAO1 PA2854 anchoring enzyme Q9HZZ0 ✗ — —

Details

Gram-negative lipoprotein-peptidoglycan tether remodelingBiological Processgram_negative_lipoprotein_peptidoglycan_tether_remodeling
peptidoglycan-protein cross-linkingGO:0018104

Connections

The covalent tether formed by the ErfK-family enzyme is the substrate for YafK/LdtF-family hydrolysis.
Part 1: outer-membrane lipoprotein anchoring to peptidoglycan
Lipoprotein-peptidoglycan tether formationReactionlipoprotein_tether_formation

Annotons

ErfK-family lipoprotein-anchoring L,D-transpeptidase
erfk_lipoprotein_anchoring
Participant: Family: ErfK-family lipoprotein-anchoring L,D-transpeptidases
Family:
ErfK-family lipoprotein-anchoring L,D-transpeptidasesPANTHER:PTHR30582:SF24
Representative Members: PSEPK PP_2320UniProtKB:Q88KH0 Pseudomonas aeruginosa PAO1 PA2854 anchoring enzymeUniProtKB:Q9HZZ0 Pseudomonas aeruginosa PA14 LdtPae2UniProtKB:A0A0H2ZCT9

Function

peptidoglycan L,D-transpeptidase activityGO:0071972
Substrates: peptidoglycan tetrapeptide stem Braun-lipoprotein-like outer-membrane lipoproteinUniProtKB:Q88KG8
Products: lipoprotein-peptidoglycan covalent tether

Processes

peptidoglycan-protein cross-linkingGO:0018104

Forms the amide bond between a peptidoglycan stem and the C terminus of an outer-membrane lipoprotein such as OprI.

Part 2: lipoprotein-peptidoglycan tether release (optional)
Lipoprotein-peptidoglycan tether hydrolysisReactionlipoprotein_tether_hydrolysis

Annotons

YafK/LdtF-family lipoprotein-tether hydrolase
yafk_lipoprotein_release
Participant: Family: YafK/LdtF-family lipoprotein-tether hydrolases
Family:
YafK/LdtF-family lipoprotein-tether hydrolasesPANTHER:PTHR36699:SF1
Representative Members: PSEPK PP_1451UniProtKB:Q88MW7 Escherichia coli DpaA/LdtF experimental exemplarUniProtKB:P0AA99 Pseudomonas aeruginosa PA14 LdtPae3 candidateUniProtKB:A0A0H2ZF55

Function

peptidoglycan-protein cross-link hydrolase activity
Substrates: lipoprotein-peptidoglycan covalent tether water
Products: released outer-membrane lipoproteinUniProtKB:Q88KG8 peptidoglycan tripeptide stem

Hydrolyzes the amide bond that joins a Braun-lipoprotein-like protein to the peptidoglycan stem.