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Step size remains robust even when one myosin head is mutant.

Muscle myosin II has two identical "heads" that really act more like hands, gripping and displacing actin to generate the force that makes a muscle contract. On page 481, Kad et al. show that only one of the two heads actually generates motion, but the second maximizes the length of the displacement.

Previous work showed that each step of a wild-type double-headed myosin displaces actin twice as far, with twice as much force, as a single-headed construct. In the new work, Kad and colleagues generated heterodimeric myosin with one wild-type head and one mutant head that can bind to actin weakly but cannot displace it. Optical trapping experiments show that this motor takes the same size steps as the wild type, so although maximal actin displacement requires two myosin heads, only one needs to be fully functional.

There are at least two explanations for this result. The weak actin-binding activity of the mutant could help to align the wild-type head to the long axis of the actin filament, much as the front wheel of a bicycle keeps the power-generating rear wheel pointing forward. Alternatively, the mutant head could function more like a bicycle frame, stabilizing the wild-type head in a maximally active conformation. The authors are now generating mutations that completely abolish actin binding activity to distinguish between these possibilities.

More subtle mutations in muscle myosin can cause human genetic disorders such as familial hypertrophic cardiomyopathy. In this disease, decreased cardiac muscle strength is linked to a point mutation in one allele, which leads to the production of heterodimeric myosin complexes with one wild-type and one moderately defective head. The authors hope to use their system to determine why this heterodimer is less efficient than wild-type homodimers.

Alan W. Dove

alanwdove{at}earthlink.net

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Related Article

A mutant heterodimeric myosin with one inactive head generates maximal displacement

Neil M. Kad, Arthur S. Rovner, Patricia M. Fagnant, Peteranne B. Joel, Guy G. Kennedy, Joseph B. Patlak, David M. Warshaw, and Kathleen M. Trybus
J. Cell Biol. 2003 162: 481-488. [Abstract] [Full Text] [PDF]

This Article PDF (Full Text) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dove, A. W. Search for Related Content PubMed Articles by Dove, A. W. Related Collections Related Article Social Bookmarking                      What's this?