Methyl-accepting Chemotaxis Proteins


The Methyl-accepting Chemotaxis Proteins (MCPs) are transmembrane signalers, but I'm giving them a separate section.  They control bacterial 'chemotaxis', that is: bacterial movement toward positive aspects of their environment, such as food, and away from negative aspects. 

I started looking at them because I assumed that they formed the evolutionary roots for human hormone and neurotransmitter receptors.  They may
have supplied a foundation for further evolution, but there seems to have been a major and sudden change at the boundary between prokaryotes and eukaryotes. 
MCPs are found only in prokaryotes.  They do not occur in eukaryotes such as the amphioxus or we humans. 


Information Processing in Bacterial Chemotaxis (Goog) 
http://stke.sciencemag.org/cgi/content/abstract/sigtrans;2002/132/pe25   
Abstract only online, but I got the PDF through the library. 
 
"...
chemotaxis by E. coli involves a signal transduction mechanism organized along the same lines as systems that mediate responses to hormones and neurotransmitters in higher eukaryotic cells


"Although the chemistry of signal transduction in bacterial and vertebrate cells differs substantially, there are numerous fundamental similarities. For example, E. coli chemotaxis receptors control the activity of an associated histidine protein kinase, CheA; eukaryotic hormone receptors control the activities of tyrosine, serine, or threonine protein kinases." 

"The two central enzymes of the E. coli chemotaxis system, the histidine kinase CheA and the response regulator CheY, are representatives of two large superfamilies that include a large  number of histidine protein kinases and response regulators ... Besides chemotaxis, these so-called “two-component systems” act to control processes ranging from cell differentiation and development to circadian rhythms and pathogenesis." 

However: 

"... the other components of the chemotaxis mechanism, including MCPs, CheW, CheR, and CheB, appear to be unique to chemotaxis signaling in prokaryotes. These proteins are not generally found in immotile bacterial species, nor have they been identified in eukaryotes."


Chemotaxis - wikidoc (Goog) 
http://www.wikidoc.org/index.php/Chemotaxis   
Long HTML.  Discusses both prokaryotic and eukaryotic chemotaxis.  "The mechanism by which eukaryotic cells chemotax is quite different from that in bacteria ...


"For the most part, eukaryotic cells sense the presence of chemotactic stimuli though the use of 7-transmembrane (or serpentine) heterotrimeric G-protein coupled receptors. This class of receptors is huge, representing a significant portion of the genome.

 

SMART: HAMP domain annotation (Goog) 

SMART: HAMP domain annotation
If you click on the "Evolution" link, it says that the HAMP domain of MCPs is found in: 

    97.83% of eubacteria (ordinary bacteria - NOT eukaryotes)  
      1.49% of archaea
      0.09%  of metazoa (including us) 



So MCPs are not directly relevant to human psychology.  However, I've spent so much time and energy researching them, and I found them so interesting, that here they are anyway. 



Universal Architecture of Bacterial Chemoreceptor Arrays (Goog) 

http://www.pnas.org/content/106/40/17181.full.pdf   
Full length PDF published in 2009, 
"Chemoreceptors are key components of the high-performance
signal transduction system that controls bacterial chemotaxis."  "...we show that chemoreceptors of different classes and in many different species representing several major bacterial phyla are all arranged into a highly conserved, 12-nm hexagonal array consistent with the proposed ‘‘trimer of dimers’’ organization." 

Diagram of a single MCP. 



"Two transmembrane regions (TM1 and TM2) anchor the receptor in the membrane. The extracellular (periplasmic) ligand-binding domain is shown in light gray.

The cytoplasmic portion of the receptor consists of the HAMP domain, linker, and the signaling domain, which, in turn, is comprised of 3 sub-domains:

    methylation regions (MR1 and MR2, white),
    the flexible bundle sub-domain (FH1 and FH2, light gray),
    and the signaling sub-domain (SR1 and SR2, dark gray).

In the E. coli Tsr receptor, Gly-340 and Gly-439 comprise the glycine ‘‘hinge’’ in the flexible bundle sub-domain, and the receptor hairpin is Gly-390."


Coupling the phosphotransferase system and the methyl-accepting chemotaxis protein-dependent chemotaxis signaling pathways of Escherichia coli (Goog) 
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC40446/pdf/pnas01503-0271.pdf   Full length PDF published in 1995. 
This is an extremely difficult article that took me several hours of careful study and re-re-reading to figure out.  I'll give a 'plain English' explanation.  You can click on the link for the technical details. 

The picture conveys the most important concept.  The MCP are just sensors, transmembrane signalers.  They're not transmembrane transporters; they don't convey anything into the cell.  The MCPs have to be linked to a transmembrane transporter for the bacteria to 'eat' the food they've found.  You can see this in the picture. 

The top row is the MCP and the chain of reactions which control the flagelllum.  The bottom row is the transmembrane transporter, labeled "EII", and the chain of reactions which allows the bacteria to injest the food, labeled "substrate-P".  I'll give a somewhat simplified 'plain English' explanation below.    



The most important letter in the diagram is "P", especially in the context of "P-".   This represents the high energy phosphate bond which is the spark of life.  Its most common provider is adenosine triphosphate (ATP) which becomes adenosine diphosphate (ADP) when it transfers its high phosphate bond to another substrate.  This is shown in the top row when ATP transfers its high energy phosphate bond to enzyme "CheA" which in turn passes it on to enzyme "CheY" which controls the rotation of the flagellum. 

In the second row, the EII transporter requires a high energy phosphate bond to function, indicating that it's probably an ABC transporter, See Transmembrane Transport in General.  This high energy phosphate bond is generated by metabolism of the injested substrate by the phosphoenolpyruvate (PEP) system.   


Making sense of it all: bacterial chemotaxis (Goog) 
http://www.bioquant.uni-heidelberg.de/fileadmin/igem/documents/literature/Wadhams2004.pdf    
Full length PDF published in 2004. 
I'm beginning to think that I may be spending too much time on bacterial chemotaxis, so I'm going to keep this brief. 

This paper came out between the two papers above: nine years after "
Coupling the phosphotransferase system..." and five years before "Universal Architecture...".  As a consequence, and as you can see in the diagram below, it has more to say about the sequence of events and less to say about the structure of the receptor. 

The capital P with a circle around it "(P)", approximately, stands for the high energy phosphate bond discussed in "Coupling...", above, and denotated there as "P-". 


Flagellar Locomotion in E. coli (Goog) 
https://www1.qiagen.com/geneglobe/PathwayView.aspx?pathwayID=184 
Single page picture. 


Evolutionary Conservation of Methyl-Accepting Chemotaxis
Protein Location in Bacteria and Archaea (Goog) 
http://jb.asm.org/cgi/reprint/182/22/6499 
Full length PDF.
"The MCPs also are localized at the poles in a more distantly related archaeon (H. salinarium)."


Structural features of methyl-accepting taxis proteins conserved between archaebacteria and eubacteria (Goog) 
http://jb.asm.org/cgi/reprint/173/18/5837    
Full length PDF. 
"Recent studies of the archaebacterium Halobacterium halobium have characterized methyl-accepting taxis proteins that in some ways resemble and in other ways differ from the analogous eubacterial proteins."  "These transmembrane proteins, often called transducers, function as receptors for specific ligands and play a crucial role in sensory adaptation.  Adaptation is mediated by changes in the extent of methylation at several specific glutamyl residues in the transducers, hence the name methyl-accepting chemotaxis protein." 


Structural studies of methyl-accepting chemotaxis proteins ... (Goog) 
Full length PDF available online for free.   



Comments