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Structural basis for the allosteric interference of myosin function by reactive thiol region mutations G680A and G680V.

ABSTRACT: The cold-sensitive single-residue mutation of glycine 680 in the reactive thiol region of Dictyostelium discoideum myosin-2 or the corresponding conserved glycine in other myosin isoforms has been reported to interfere with motor function. Here we present the x-ray structures of myosin motor domain mutants G680A in the absence and presence of nucleotide as well as the apo structure of mutant G680V. Our results show that the Gly-680 mutations lead to uncoupling of the reactive thiol region from the surrounding structural elements. Structural and functional data indicate that the mutations induce the preferential population of a state that resembles the ADP-bound state. Moreover, the Gly-680 mutants display greatly reduced dynamic properties, which appear to be related to the recovery of myosin motor function at elevated temperatures.

SUBMITTER: Preller M

PROVIDER: S-EPMC3186370 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Structural basis for the allosteric interference of myosin function by reactive thiol region mutations G680A and G680V.

Preller Matthias M Bauer Stefanie S Adamek Nancy N Fujita-Becker Setsuko S Fedorov Roman R Geeves Michael A MA Manstein Dietmar J DJ

The Journal of biological chemistry 20110813 40

The cold-sensitive single-residue mutation of glycine 680 in the reactive thiol region of Dictyostelium discoideum myosin-2 or the corresponding conserved glycine in other myosin isoforms has been reported to interfere with motor function. Here we present the x-ray structures of myosin motor domain mutants G680A in the absence and presence of nucleotide as well as the apo structure of mutant G680V. Our results show that the Gly-680 mutations lead to uncoupling of the reactive thiol region from t ...[more]

PMID: 21841195

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