2be6
From Proteopedia
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2.0 A crystal structure of the CaV1.2 IQ domain-Ca/CaM complex
Contents |
Overview
Changes in activity-dependent calcium flux through voltage-gated calcium, channels (Ca(V)s) drive two self-regulatory calcium-dependent feedback, processes that require interaction between Ca(2+)/calmodulin (Ca(2+)/CaM), and a Ca(V) channel consensus isoleucine-glutamine (IQ) motif:, calcium-dependent inactivation (CDI) and calcium-dependent facilitation, (CDF). Here, we report the high-resolution structure of the, Ca(2+)/CaM-Ca(V)1.2 IQ domain complex. The IQ domain engages hydrophobic, pockets in the N-terminal and C-terminal Ca(2+)/CaM lobes through sets of, conserved 'aromatic anchors.' Ca(2+)/N lobe adopts two conformations that, suggest inherent conformational plasticity at the Ca(2+)/N lobe-IQ domain, interface. Titration calorimetry experiments reveal competition between, the lobes for IQ domain sites. Electrophysiological examination of, Ca(2+)/N lobe aromatic anchors uncovers their role in Ca(V)1.2 CDF., Together, our data suggest that Ca(V) subtype differences in CDI and CDF, are tuned by changes in IQ domain anchoring positions and establish a, framework for understanding CaM lobe-specific regulation of Ca(V)s.
Disease
Known diseases associated with this structure: Timothy syndrome OMIM:[114205]
About this Structure
2BE6 is a Protein complex structure of sequences from Homo sapiens with CA and NI as ligands. Full crystallographic information is available from OCA.
Reference
Insights into voltage-gated calcium channel regulation from the structure of the CaV1.2 IQ domain-Ca2+/calmodulin complex., Van Petegem F, Chatelain FC, Minor DL Jr, Nat Struct Mol Biol. 2005 Dec;12(12):1108-15. Epub 2005 Nov 20. PMID:16299511
Page seeded by OCA on Mon Nov 12 21:01:38 2007
