X-ray crystal structure of a TRPM assembly domain reveals an antiparallel four-stranded coiled-coil.
Transient receptor potential (TRP) channels comprise a large family of tetrameric cation-selective ion channels that respond to diverse forms of sensory input. Earlier studies showed that members of the TRPM subclass possess a self-assembling tetrameric C-terminal cytoplasmic coiled-coil domain that underlies channel assembly and trafficking. Here, we present the high-resolution crystal structure of the coiled-coil domain of the channel enzyme TRPM7. The crystal structure, together with biochemical experiments, reveals an unexpected four-stranded antiparallel coiled-coil architecture that bears unique features relative to other antiparallel coiled-coils. Structural analysis indicates that a limited set of interactions encode assembly specificity determinants and uncovers a previously unnoticed segregation of TRPM assembly domains into two families that correspond with the phylogenetic divisions seen for the complete subunits. Together, the data provide a framework for understanding the mechanism of TRPM channel assembly and highlight the diversity of forms found in the coiled-coil fold.
Fujiwara
Yuichiro
Y
Cardiovascular Research Institute, Departments of Biochemistry and Biophysics and Cellular and Molecular Pharmacology, California Institute for Quantitative Biosciences, University of California San Francisco, San Francisco, CA 94158-2330, USA.
Minor
Daniel L
DL
D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016415:Sequence Alignment; D012996:Solutions / Q000737:chemistry; D055672:Static Electricity; D050053:TRPM Cation Channels / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism
D021122:Protein Subunits; D012996:Solutions; D050053:TRPM Cation Channels; C486584:Trpm7 protein, rat
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