Crystal structure of the chemotaxis receptor methyltransferase CheR suggests a conserved structural motif for binding S-adenosylmethionine.
BACKGROUND
Flagellated bacteria swim towards favorable chemicals and away from deleterious ones. The sensing of chemoeffector gradients involves chemotaxis receptors, transmembrane proteins that detect stimuli through their periplasmic domains and transduce signals via their cytoplasmic domains to the downstream signaling components. Signaling outputs from chemotaxis receptors are influenced both by the binding of the chemoeffector ligand to the periplasmic domain and by methylation of specific glutamate residues on the cytoplasmic domain of the receptor. Methylation is catalyzed by CheR, an S-adenosylmethionine-dependent methyltransferase. CheR forms a tight complex with the receptor by binding a region of the receptors that is distinct from the methylation site. CheR belongs to a broad class of enzymes involved in the methylation of a variety of substrates. Until now, no structure from the class of protein methyltransferases has been characterized.


RESULTS
The structure of the Salmonella typhimurium chemotaxis receptor methyltransferase CheR bound to S-adenosylhomocysteine, a product and inhibitor of the methylation reaction, has been determined at 2.0 A resolution. The structure reveals CheR to be a two-domain protein, with a smaller N-terminal helical domain linked through a single polypeptide connection to a larger C-terminal alpha/beta domain. The C-terminal domain has the characteristics of a nucleotide-binding fold, with an insertion of a small antiparallel beta sheet subdomain. The S-adenosylhomocysteine-binding site is formed mainly by the large domain, with contributions from residues within the N-terminal domain and the linker region.


CONCLUSIONS
The CheR structure shares some structural similarities with small molecule DNA and RNA methyltransferases, despite a lack of sequence similarity among them. In particular, there is significant structural preservation of the S-adenosylmethionine-binding clefts; the specific length and conformation of a loop in the alpha/beta domain seems to be required for S-adenosylmethionine binding within these enzymes. Unique structural features of CheR, such as the beta subdomain, are probably necessary for CheR's specific interaction with its substrates, the bacterial chemotaxis receptors.
Djordjevic
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Howard Hughes Medical, Institute Center for Advanced Biotechnology and Medicine, Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey, 08854, USA.
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D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D046911:Macromolecular Substances; D008780:Methyltransferases / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000201:enzymology*; D017386:Sequence Homology, Amino Acid; D012984:Software; D055672:Static Electricity
D046911:Macromolecular Substances; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D008780:Methyltransferases; C038706:chemotaxis methyltransferase