Essential Ca(V)beta modulatory properties are AID-independent.
Voltage-gated Ca(2+) channel beta (Ca(v)beta) subunits have a highly conserved core consisting of interacting Src homology 3 and guanylate kinase domains, and are postulated to exert their effects through AID, the major interaction site in the pore-forming alpha(1) subunit. This stereotypical interaction does not explain how individual Ca(v)beta subunits modulate alpha(1) subunits differentially. Here we show that AID is neither necessary nor sufficient for critical Ca(v)beta regulatory properties. Complete modulation depends on additional contacts that are exclusive of AID and not revealed in recent crystal structures. These data offer a new context for understanding Ca(v)beta modulation, suggesting that the AID interaction orients the Ca(v)beta core so as to permit additional isoform-specific Ca(v)alpha(1)-Ca(v)beta interactions that underlie the particular regulation seen with each Ca(v)alpha(1)-Ca(v)beta pair, rather than as the main site of regulation.
Maltez
Janet M
JM
Department of Pharmacology, Columbia University, New York, New York 10032, USA.
Nunziato
Deborah A
DA
Kim
James
J
Pitt
Geoffrey S
GS
D000818:Animals; D015220:Calcium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004594:Electrophysiology; D051528:Guanylate Kinases; D007700:Kinetics; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D014982:Xenopus laevis; D018909:src Homology Domains
D015220:Calcium Channels; D021122:Protein Subunits; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases