CtpM (PA2652) is a methyl-accepting chemotaxis protein (MCP) of Pseudomonas aeruginosa PAO1 that serves as the chemoreceptor for L-malate and related C4-dicarboxylic acids. It is an inner-membrane receptor with two transmembrane helices flanking a periplasmic sCache_2 ligand binding domain, followed by a cytoplasmic HAMP domain and the MCP signalling domain. The ligand binding domain is a dimer and directly binds five C4-dicarboxylic acids (L-malate, citramalate, citraconate, bromosuccinate and methylsuccinate) with micromolar to millimolar affinities. Three of these act as chemoattractants and two as antagonists that compete for the binding site and dampen signalling. CtpM signals through the Che chemosensory pathway, and a ctpM mutant loses chemotaxis to malate. Its role was first revealed in an aer mutant, in which Aer-mediated energy taxis no longer masks malate chemotaxis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004888 transmembrane signaling receptor activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO transmembrane signaling receptor activity from the chemotaxis methyl-accepting receptor signature. Reason: Core function. The periplasmic ligand binding domain binds C4-dicarboxylic acids directly and the receptor mediates chemotaxis to them through the cytoplasmic Che pathway, which is transmembrane signaling receptor activity. Supporting Evidence: PMID:29391435 the ligand binding domain (LBD) of the chemoreceptor PA2652 directly recognizes five C4-dicarboxylic acids PMID:29391435 we found that only the che pathway is involved in PA2652-mediated taxis |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Plasma membrane from the UniProt subcellular location (cell inner membrane, multi-pass). Reason: Two predicted transmembrane helices bracket the periplasmic sCache_2 ligand binding domain, the standard topology of an inner-membrane chemoreceptor. Supporting Evidence: file:PSEAE/ctpM/ctpM-uniprot.txt Cell inner membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000255}. |
| GO:0006935 chemotaxis | IBA GO_REF:0000033 | TOO GENERAL | Summary: Chemotaxis propagated from PAINT node PTN001280296 (PTHR32089 MCP clade, 215 leaves in 22 taxa). CtpM is itself one of the ten IBD seeds through its PseudoCAP IMP rows. Reason: True, but GO:0050918 positive chemotaxis, accepted on this gene, is an is_a descendant and entails it. The IBD itself is sound - it is grounded in several independent experimentally characterized MCPs (B. subtilis McpC, the HemAT transducers) - and the target's presence in WITH/FROM reflects its own experimental row, which is expected, not circular. Supporting Evidence: PMID:17933940 We identified PA2652 as a chemoreceptor for malate by screening aer mcp double mutants by using swarm plate assays. PMID:29391435 Quantitative chemotaxis assays of the mutant strain toward 10 mM ligand solutions showed a dramatic reduction in chemotaxis for all ligands |
| GO:0006935 chemotaxis | IEA GO_REF:0000120 | TOO GENERAL | Summary: Combined InterPro/ARBA chemotaxis assignment for an MCP-family protein. Reason: True, but GO:0050918 positive chemotaxis, accepted on this gene, is an is_a descendant and entails it. Supporting Evidence: PMID:29391435 Quantitative chemotaxis assays of the mutant strain toward 10 mM ligand solutions showed a dramatic reduction in chemotaxis for all ligands |
| GO:0006935 chemotaxis | IMP PMID:17933940 Identification of a malate chemoreceptor in Pseudomonas aeru... | TOO GENERAL | Summary: PseudoCAP IMP seed for the PAINT IBD at PTN001280296. The abstract states that PA2652 was identified as the malate chemoreceptor by screening aer mcp double mutants in swarm plate assays; the follow-up paper reports that this mutant did not respond to malate. Reason: Seed verdict SOUND, but the row is entailed by GO:0050918 positive chemotaxis (is_a chemotaxis), accepted on this gene from the same paper. Loss of malate chemotaxis in the receptor mutant, for a receptor whose ligand binding domain was later shown to bind malate directly (PMID:29391435), shows that CtpM does the sensing step of chemotaxis. Swarm plates alone could reflect motility, but the defect was specific to malate in an aer background, and the later quantitative capillary assays confirm it. Supporting Evidence: PMID:17933940 We identified PA2652 as a chemoreceptor for malate by screening aer mcp double mutants by using swarm plate assays. PMID:29391435 The study that reported its initial identification showed that a mutant in this gene did not respond to malate |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO signal transduction from the HAMP and MCP signalling domains. Reason: Correct but general. CtpM binds its ligands in the periplasm and signals across the inner membrane, so the more specific term is cell surface receptor signaling pathway (an is_a descendant), as used for other transmembrane MCPs. Proposed replacements: cell surface receptor signaling pathway Supporting Evidence: file:PSEAE/ctpM/ctpM-uniprot.txt Chemotactic-signal transducers respond to changes in the concentration of attractants and repellents in the environment, transduce a signal from the outside to the inside of the cell PMID:29391435 the ligand binding domain (LBD) of the chemoreceptor PA2652 directly recognizes five C4-dicarboxylic acids |
| GO:0016020 membrane | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO membrane location. Reason: True but uninformative; GO:0005886 plasma membrane, accepted on this gene, is an is_a descendant and entails it. Supporting Evidence: file:PSEAE/ctpM/ctpM-uniprot.txt Cell inner membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000255}. |
| GO:0050918 positive chemotaxis | IMP PMID:17933940 Identification of a malate chemoreceptor in Pseudomonas aeru... | ACCEPT | Summary: PseudoCAP IMP; malate is an attractant and the ctpM mutant loses attraction to it. Reason: Malate, bromosuccinate and citramalate are chemoattractants sensed by CtpM, so positive chemotaxis is the precise process; it is an is_a descendant of the chemotaxis rows. Supporting Evidence: PMID:29391435 In vivo experimentation showed that three of the identified ligands act as chemoattractants PMID:29391435 The study that reported its initial identification showed that a mutant in this gene did not respond to malate |
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Download this section (compressed HTML)Q: GO has no molecular function term for C4-dicarboxylate (malate) binding by a sensor domain. Would a term such as L-malate binding be useful for chemoreceptors and sensor kinases such as CtpM and DctB?
Experiment: Determine the structure of the CtpM sCache_2 domain with L-malate and with the antagonist methylsuccinate, to see how antagonist binding fails to produce the signalling conformation.
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