Timothy mutation affects tightly sealing point of CaV1.2 activation gate
نویسندگان
چکیده
Results Homology modeling revealed that G432 forms part of a highly conserved structure motif (G/A/G/A) of small residues in homologous positions of all four domains (G432 (IS6), A780 (IIS6), G1193 (IIIS6), A1503 (IVS6)). In contrast, corresponding mutations in domains II, III and IV induced parallel shifts of activation and inactivation curves indicating a preserved coupling between both processes. Disruption between coupling of activation and inactivation was specific for mutations of G432 in domain I. Mutations of G432 removed inactivation irrespective of the changes in activation. In all four domains residues G/A/G/A are in close contact with larger bulky amino acids from neighboring S6 helices.
منابع مشابه
Timothy Mutation Disrupts the Link between Activation and Inactivation in CaV1.2 Protein*
The Timothy syndrome mutations G402S and G406R abolish inactivation of Ca(V)1.2 and cause multiorgan dysfunction and lethal arrhythmias. To gain insights into the consequences of the G402S mutation on structure and function of the channel, we systematically mutated the corresponding Gly-432 of the rabbit channel and applied homology modeling. All mutations of Gly-432 (G432A/M/N/V/W) diminished ...
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