Mutations of nonconserved residues within the calcium channel alpha1-interaction domain inhibit beta-subunit potentiation.

The Journal of General Physiology
Giovanni Gonzalez-GutierrezAlan Neely

Abstract

Voltage-dependent calcium channels consist of a pore-forming subunit (Ca(V)alpha(1)) that includes all the molecular determinants of a voltage-gated channel, and several accessory subunits. The ancillary beta-subunit (Ca(V)beta) is a potent activator of voltage-dependent calcium channels, but the mechanisms and structural bases of this regulation remain elusive. Ca(V)beta binds reversibly to a conserved consensus sequence in Ca(V)alpha(1), the alpha(1)-interaction domain (AID), which forms an alpha-helix when complexed with Ca(V)beta. Conserved aromatic residues face to one side of the helix and strongly interact with a hydrophobic pocket on Ca(V)beta. Here, we studied the effect of mutating residues located opposite to the AID-Ca(V)beta contact surface in Ca(V)1.2. Substitution of AID-exposed residues by the corresponding amino acids present in other Ca(V)alpha(1) subunits (E462R, K465N, D469S, and Q473K) hinders Ca(V)beta's ability to increase ionic-current to charge-movement ratio (I/Q) without changing the apparent affinity for Ca(V)beta. At the single channel level, these Ca(V)1.2 mutants coexpressed with Ca(V)beta(2a) visit high open probability mode less frequently than wild-type channels. On the other hand, Ca(V)1.2 car...Continue Reading

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Citations

Oct 21, 2010·Physiological Reviews·Zafir Buraei, Jian Yang
Feb 27, 2015·Journal of Pediatric Endocrinology & Metabolism : JPEM·Shira HarelWilliam T Gibson
Jan 21, 2012·Biophysical Journal·Wanchana JangsangthongStefan Herzig

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Methods Mentioned

BETA
PCR

Software Mentioned

MDS
pCLAMP

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