Long single α-helical tail domains bridge the gap between structure and function of myosin VI

Benjamin J. Spink, Sivaraj Sivaramakrishnan, Jan Lipfert, Sebastian Doniach, James A. Spudich

Research output: Contribution to journalArticlepeer-review

95 Scopus citations


Myosin VI has challenged the lever arm hypothesis of myosin movement because of its ability to take ∼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 α-helix of ∼10 nm, which is anchored to the calmodulin-bound IQ domain by a globular proximal tail. With the medial tail contributing to the ∼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.

Original languageEnglish (US)
Pages (from-to)591-597
Number of pages7
JournalNature Structural and Molecular Biology
Issue number6
StatePublished - Jun 2008
Externally publishedYes

Bibliographical note

Funding Information:
We thank A. Dunn, Z. Bryant and N. Geething of Stanford University for technical help with protein purification and motility assays, critical discussions and manuscript review; H.L. Sweeney of the University of Pennsylvania for plasmids; K. Holmes of the Max Planck Institute for Medical Research, Heidelberg, for the acto-myosin PDB model; T. Fenn of Stanford University for technical help with MALS analysis and graphical presentation; T. Purcell of the University of California, San Fransisco, for help with model building; S. Seifert of the Advanced Photon Source; R. Fenn of Stanford University for help with SAXS data collection; and S. Patel of Stanford University for MALDI analysis. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. B.J.S. is partially supported by grant T32 GM008294; S.D. is supported by grant PO1 GM066275; and J.A.S. is supported by grant GM33289, all from the US National Institutes of Health.


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