Interhead distance measurements in myosin VI via SHRImP support a simplified hand-over-hand model

¹ University of Illinois
² University of Pennsylvania

^* To whom correspondence should be addressed. E-mail: selvin{at}uiuc.edu.

Submitted on February 3, 2005
Revised on March 17, 2005
Accepted on 26 April 2005

	Abstract

Myosin-VI walks in a hand-over-hand fashion with an average step size of 30 nm, which is much larger than its 10 nm lever arm. Recent experiments suggest that myosin VI structure has an unfolded and flexible region in the proximal tail which makes such a large step possible. In addition, cryo-EM images of actomyosin-VI show the two heads bound to the actin monomers with a broad distribution of distances, including some as close as a few nanometers. This observation when combined with the existence of a flexible region in the structure, which takes part in stepping, challenged the hand-over-hand model. In the hand-over-hand model the lever arm is considered to be rigid and the inter-head separation should not be very different from 30 nm. We considered an alternative model in which myosin-VI heads sequentially take 60 nm steps while the inter-head separation alternates between a large and small value (x and 60-x, where x<30). In order to clarify these issues, we used a new technique, SHRImP, to measure the inter-head distance of nearly rigor myosin-VI molecules. Our data shows a single peak at 29.3±0.7 nm, in agreement with the straightforward hand-over-hand model.

Key Words: fluoresence, myosin VI, single molecule

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