Crystal structure of the human TRPV2 channel ankyrin repeat domain.
TRPV channels are important polymodal integrators of noxious stimuli mediating thermosensation and nociception. An ankyrin repeat domain (ARD), which is a common protein-protein recognition domain, is conserved in the N-terminal intracellular domain of all TRPV channels and predicted to contain three to four ankyrin repeats. Here we report the first structure from the TRPV channel subfamily, a 1.7 A resolution crystal structure of the human TRPV2 ARD. Our crystal structure reveals a six ankyrin repeat stack with multiple insertions in each repeat generating several unique features compared with a canonical ARD. The surface typically used for ligand recognition, the ankyrin groove, contains extended loops with an exposed hydrophobic patch and a prominent kink resulting from a large rotational shift of the last two repeats. The TRPV2 ARD provides the first structural insight into a domain that coordinates nociceptive sensory transduction and is likely to be a prototype for other TRPV channel ARDs.
McCleverty
Clare J
CJ
Genomics Institute of the Novartis Research Foundation, CA 92121, USA.
Koesema
Eric
E
Patapoutian
Ardem
A
Lesley
Scott A
SA
Kreusch
Andreas
A
D000595:Amino Acid Sequence; D017089:Ankyrin Repeat; D001665:Binding Sites; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D050916:TRPV Cation Channels / Q000737:chemistry* / Q000235:genetics*
D050916:TRPV Cation Channels