Extension of a three-helix bundle domain of myosin VI and key role of calmodulins

Yanxin Liu, Jen Hsin, Hyeong Jun Kim, Paul R. Selvin, Klaus Schulten

Research output: Contribution to journalArticle

Abstract

The molecular motor protein myosin VI moves toward the minus-end of actin filaments with a step size of 30-36 nm. Such large step size either drastically limits the degree of complex formation between dimer subunits to leave enough length for the lever arms, or requires an extension of the lever arms' crystallographically observed structure. Recent experimental work proposed that myosin VI dimerization triggers the unfolding of the protein's proximal tail domain which could drive the needed lever-arm extension. Here, we demonstrate through steered molecular dynamics simulation the feasibility of sufficient extension arising from turning a three-helix bundle into a long α-helix. A key role is played by the known calmodulin binding that facilitates the extension by altering the strain path in myosin VI. Sequence analysis of the proximal tail domain suggests that further calmodulin binding sites open up when the domain's three-helix bundle is unfolded and that subsequent calmodulin binding stabilizes the extended lever arms.

Original languageEnglish (US)
Pages (from-to)2964-2973
Number of pages10
JournalBiophysical journal
Volume100
Issue number12
DOIs
StatePublished - Jan 1 2011

ASJC Scopus subject areas

  • Biophysics

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