title: Extension of a three-helix bundle domain of myosin VI and key role of calmodulins.
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.
authors.affiliation: Department of Physics and Center for the Physics of Living Cells, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Liu
authors.forename: Jen
authors.initials: J
authors.lastname: Hsin
authors.forename: HyeongJun
authors.initials: H
authors.lastname: Kim
authors.forename: Paul R
authors.initials: PR
authors.lastname: Selvin
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulten
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry; D000199:Actins / Q000737:chemistry; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002147:Calmodulin / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D018995:Myosin Heavy Chains / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D000199:Actins; D002147:Calmodulin; C089785:myosin VI; D018995:Myosin Heavy Chains