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The Mechanism of Myosins

The myosins are a huge family of actin binding proteins whose function it is to move relative to the actin microfilament.  The number of myosins continues to increase, and the nomenclature can be difficult but fortunately there is an excellent site operated from the MRC-LMB in Cambridge by Tony Hodge, Jamie Cope and John Kendrick Jones.  The mechanism by which myosin changes shape to effect contraction has been surrounded by a series of very contentious issues.  The problem  has seen the application of some very impressive technology involving measurement of single molecular interactions, perhaps the first time in the whole of biology that this has been accomplished?   On the other hand this field has been hampered and distracted to some extent by polarization of personal opinion.  

Step Size
There continues to be a debate as to how far each  ATP-hydrolysis cycle takes the myosin molecule with  respect to the actin filament (the step-size).  It is widely held that the myosin head produces small changes in conformation upon the hydrolysis of ATP.  This small change in shape is then amplified by the so called neck or lever arm.  This lever arm is an a-helix often supported by light chains. Several groups have tried to answer the question of what determines the step size by using myosin-V. The length of the myosin-V lever arm is determined by the IQ motifs and this in turn is thought to determine the overall transport velocity (Schott et al, 2002).  Experiments in which the natural myosin V gene of Saccharomyces was replaced by cDNAs encoding myosin Vs with reduced or increased numbers of IQ repeats (and thus lever arm length) concluded that the longer this arm the faster the transport velocity in vivo  (Schott et al, 2002) the step size of 25nm results from the repeated orientation of actin monomers within the actin filament.  It will be interesting to test the myosin V IQ series of mutants generated by the Bretscher group in the sophisticated apparatus used by the Molloy group (Veigel et al, 2001) . 



Moore, J. R., Krementsova, E. B., Trybus, K. M. & Warshaw, D. M. (2001) Myosin V exhibits a high duty cycle and large unitary displacement., J.Cell Biol. 155, 625-635.

Rock, R. S., Rice, S. E., Wells, A. L., Purcell, T. J., Spudich, J. A. & Sweeney, H. L. (2001) Myosin VI is a processive motor with a large step size, PNAS. 98, 13655-13659.

Schott, D. H., Collins, R. N. & Bretscher, A. (2002) Secretory vesicle transport velocity in living cells depends on the myosin-V lever arm length., J.Cell Biol. 156, 35-39.

Shih, W.M., Gryczynski, Z., Lakowicz, J.R., & Spudich, J.A. (2000). "A FRET-based sensor reveals large ATP hydrolysis-induced conformational changes and three distinct states of the molecular motor myosin." Cell 102, 683-694.

Tanaka, H., Homma, K., Iwane, A. H., Katayama, E., Ikebe, R., Saito, J., Yanagida, T. & Ikebe, M. (2002) The motor domain determines the large step size of myosin-V., Nature. 415, 192-195.

Veigel, C., Wang, F., Bartoo, M. L., Sellers, J. R. & Molloy, J. E. (2002) The gated gait of the processive molecular motor, myosin V., Nature Cell Biol. 4, 59-65.

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