View source for Methyl-accepting chemotaxis proteins

{{short description|Family of bacterial transmembrane receptors}}
{{citations needed|date=April 2024}}
{{Infobox protein family
| Symbol = MCPsignal
| Name = MCPsignal
| image = 3zx6.png
| width =
| caption = Methyl-accepting chemotaxis protein I. PDB entry {{PDBe|3zx6}}<ref>{{Cite journal | doi = 10.1016/j.jsb.2014.03.015| pmid = 24680785| title = Axial helix rotation as a mechanism for signal regulation inferred from the crystallographic analysis of the E. Coli serine chemoreceptor| journal = Journal of Structural Biology| volume = 186| issue = 3| pages = 349–356| year = 2014| last1 = Ferris | first1 = H. U. | last2 = Zeth | first2 = K. | last3 = Hulko | first3 = M. | last4 = Dunin-Horkawicz | first4 = S. | last5 = Lupas | first5 = A. N. | doi-access = free }}</ref>
| Pfam = PF00015
| Pfam_clan = CL0510
| InterPro = IPR004089
| SMART =
| PROSITE = PDOC00465
| MEROPS =
| SCOP = 1qu7
| TCDB =
| OPM family =
| OPM protein =
| CAZy =
| CDD = cd11386
}}
{{Pfam_box
| Symbol = Methyl-accepting chemotaxis proteins (MCP)
| Name = Methyl-accepting chemotaxis proteins
| image = Ligand binding domain aspartate receptor.png
| width = 200
| caption = [[Ribbon diagram]] of the ''S. typhimurium'' aspartate receptor ligand binding domain<ref name="pmid8831788">{{PDB|1VLT}}; {{cite journal |vauthors=Yeh JI, Biemann HP, Privé GG, Pandit J, Koshland DE Jr, Kim SH | title =High-resolution structures of the ligand binding domain of the wild-type bacterial aspartate receptor| journal = J Mol Biol | volume = 262 | pages = 186–201| year = 1996 | issue =2| pmid = 8831788 | doi=10.1006/jmbi.1996.0507}}; rendered with [http://pymol.sourceforge.net PyMOL]</ref>
| Pfam= PF02203
| InterPro= IPR004090
| SMART=  TarH
| Prosite =
| SCOP = 1lih
| TCDB =
| OPM family=
| OPM protein=
| CDD = cd00181
| PDB=
}}
The '''methyl-accepting chemotaxis proteins''' ('''MCP''', also '''aspartate receptor''') are a family of [[cell surface receptor|transmembrane receptors]] that mediate [[chemotaxis|chemotactic]] response in certain [[gut flora|enteric bacteria]], such as ''[[Salmonella enterica enterica]]'' and ''[[Escherichia coli]]''.<ref name="PUB00013522">{{cite journal |vauthors=Kim SH, Prive GG, Pandit J, Koshland DE, Yeh JI, Biemann HP |title=High-resolution structures of the ligand binding domain of the wild-type bacterial aspartate receptor |journal=J. Mol. Biol. |volume=262 |issue=2 |pages=186–201 |year=1996 |pmid=8831788 |doi=10.1006/jmbi.1996.0507}}</ref> These methyl-accepting chemotaxis receptors are one of the first components in the sensory excitation and adaptation responses in bacteria, which act to alter swimming behaviour upon detection of specific chemicals. Use of the MCP allows bacteria to detect concentrations of molecules in the [[extracellular matrix]] so that the bacteria may smooth swim or tumble accordingly. If the bacterium detects rising levels of attractants ([[nutrient]]s) or declining levels of repellents ([[toxin]]s), the bacterium will continue swimming forward, or smooth swimming. If the bacterium detects declining levels of attractants or rising levels of repellents, the bacterium will tumble and re-orient itself in a new direction. In this manner, a bacterium may swim towards nutrients and away from toxins<ref name="pmid16359703">{{cite journal |vauthors=Derr P, Boder E, Goulian M | title = Changing the specificity of a bacterial chemoreceptor | journal = J. Mol. Biol. | volume = 355 | issue = 5 | pages = 923–32 |date=February 2006 | pmid = 16359703 | doi = 10.1016/j.jmb.2005.11.025 }}</ref>
== Evolution ==
There are many different types of bacterial 60 kDa transmembrane receptors, which share similar topology and signalling mechanisms. They possess three domains: a periplasmic ligand-binding domain, two transmembrane segments, and a cytoplasmic domain. The structure of the ligand-binding domain comprises a closed or partly opened, four-helical bundle with a left-handed twist. The difference in the sequence of the ligand-binding domain between receptors reflects the different ligand specificities. Binding of the ligand causes a conformational change that is transmitted across the membrane to the cytoplasmic activation domain.<ref name="PUB00013523">{{cite journal |vauthors=Koshland DE, Yu EW |title=Propagating conformational changes over long (and short) distances in proteins |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue=17 |pages=9517–9520 |year=2001 |pmid=11504940 |doi=10.1073/pnas.161239298 |pmc=55484|bibcode=2001PNAS...98.9517Y |url=https://works.bepress.com/edward_yu/3/download/ |doi-access=free }}</ref>
Environmental diversity gives rise to diversity in [[bacterial]] [[cell signalling|signalling]] receptors, and consequently there are many [[genes]] encoding MCPs.<ref name="pmid17299051">{{cite journal |vauthors=Alexander RP, Zhulin IB | title = Evolutionary genomics reveals conserved structural determinants of signaling and adaptation in microbial chemoreceptors | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 104 | issue = 8 | pages = 2885–90 |date=February 2007 | pmid = 17299051 | pmc = 1797150 | doi = 10.1073/pnas.0609359104 | doi-access = free }}</ref> For example, there are four well-characterised MCPs found in ''Escherichia coli'': Tar (taxis towards [[aspartate]] and maltose, away from [[nickel]] and cobalt), Tsr (taxis towards serine, away from leucine, indole and weak acids), Trg (taxis towards [[galactose]] and ribose) and Tap (taxis towards dipeptides).
== Structure ==
MCPs share similar structure and [[cell signaling|signalling]] mechanism. MCPs form [[Protein dimer|dimers]]. Three dimers of MCP spontaneously form trimers. Trimers are complexed by CheA and CheW into hexagonal lattices. MCPs either [[Molecular binding|bind]] [[ligands]] directly or [[Protein-protein interaction|interact]] with [[ligand (biochemistry)|ligand-binding]] proteins, transducing the signal to downstream signalling proteins in the [[cytoplasm]]. Most MCPs contain: (a) an N-terminal [[signal peptide]] that is a [[transmembrane alpha-helix]] in the mature protein; (b) a poorly-conserved periplasmic [[Receptor (biochemistry)|receptor]] (ligand-binding) domain; (c) a transmembrane alpha-helix; (d) generally one or more HAMP domains and (e) a [[conservation (genetics)|highly conserved]] C-terminal cytoplasmic domain that [[Protein-protein interaction|interact]]s with downstream signalling components. The C-terminal domain contains the [[methylated]] [[glutamate]] [[Residue (chemistry)|residue]]s.
MCPs undergo two [[covalent]] modifications: deamidation and reversible [[methylation]] at a number of [[glutamic acid|glutamate]] [[Residue (chemistry)|residue]]s. Attractants increase the level of methylation, while repellents decrease it. The [[methyl group]]s are added by the methyl-transferase CheR and are removed by the methylesterase CheB.
== Function ==
Binding a [[ligand]] causes a [[conformational change]] in the MCP receptor which translates down the hairpin structure and inhibits its sensor kinase. At the tip of the hairpin are two proteins that associate to the MCP: CheW and CheA. CheA acts as the sensor [[kinase]]. CheA has kinase activity and autophosphorylates itself on a histidyl residue when activated by the MCP. CheW is believed to be a transducer of the signal from the MCP to CheA. Activated CheA transfers its phosphoryl group to CheY, a response regulator. Phosphorylated CheY  phosphorylates the basal body FliM which is connected to the [[flagellum]]. [[Phosphorylation]] of the basal body acts as a flagellar switch and changes the direction of rotation of the flagellum. This change in direction allows for alternation between smooth swimming and tumbling which biases the bacterial random walk towards attractant.
==References==
{{reflist}}
{{Commons category|Methyl-accepting chemotaxis protein}}
{{InterPro content|IPR004089}}
{{InterPro content|IPR003122}}
[[Category:Bacterial proteins]]
[[Category:Transmembrane receptors]]
[[Category:Protein families]]
[[Category:Protein domains]]