Full-length myosin VI dimerizes and moves processively along actin filaments upon monomer clustering.
Myosin VI is a reverse direction actin-based motor capable of taking large steps (30-36 nm) when dimerized. However, all dimeric myosin VI molecules so far examined have included non-native coiled-coil sequences, and reports on full-length myosin VI have failed to demonstrate the existence of dimers. Herein, we demonstrate that full-length myosin VI is capable of forming stable, processive dimers when monomers are clustered, which move up to 1-2 mum in approximately 30 nm, hand-over-hand steps. Furthermore, we present data consistent with the monomers being prevented from dimerizing unless they are held in close proximity and that dimerization is somewhat inhibited by the cargo binding tail. A model thus emerges that cargo binding likely clusters and initiates dimerization of full-length myosin VI molecules. Although this mechanism has not been previously described for members of the myosin superfamily, it is somewhat analogous to the proposed mechanism of dimerization for the kinesin Unc104.
Park
Hyokeun
H
Department of Chemistry, University of Illinois, Urbana, Illinois 61801, USA.
Ramamurthy
Bhagavathi
B
Travaglia
Mirko
M
Safer
Dan
D
Chen
Li-Qiong
LQ
Franzini-Armstrong
Clara
C
Selvin
Paul R
PR
Sweeney
H Lee
HL
D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D019281:Dimerization; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D020836:Protein Structure, Quaternary; D013552:Swine
D000199:Actins; C089785:myosin VI; D000251:Adenosine Triphosphatases; D018995:Myosin Heavy Chains