Long single alpha-helical tail domains bridge the gap between structure and function of myosin VI.
Myosin VI has challenged the lever arm hypothesis of myosin movement because of its ability to take approximately 36-nm steps along actin with a canonical lever arm that seems to be too short to allow such large steps. Here we demonstrate that the large step of dimeric myosin VI is primarily made possible by a medial tail in each monomer that forms a rare single alpha-helix of approximately 10 nm, which is anchored to the calmodulin-bound IQ domain by a globular proximal tail. With the medial tail contributing to the approximately 36-nm step, rather than dimerizing as previously proposed, we show that the cargo binding domain is the dimerization interface. Furthermore, the cargo binding domain seems to be folded back in the presence of the catalytic head, constituting a potential regulatory mechanism that inhibits dimerization.
Department of Biochemistry, Stanford University, 279 Campus Drive, Stanford, California 94305, USA.
Benjamin J
BJ
Spink
Sivaraj
S
Sivaramakrishnan
Jan
J
Lipfert
Sebastian
S
Doniach
James A
JA
Spudich
D002147:Calmodulin; D003001:Cloning, Molecular; D019281:Dimerization; D006801:Humans; D020409:Molecular Motor Proteins; D009038:Motion; D018995:Myosin Heavy Chains / Q000737:chemistry* / Q000502:physiology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D002147:Calmodulin; D020409:Molecular Motor Proteins; C089785:myosin VI; D018995:Myosin Heavy Chains