The unique insert at the end of the myosin VI motor is the sole determinant of directionality.
Myosin VI moves toward the pointed (minus) end of actin filaments, the reverse direction of other myosin classes. The myosin VI structure demonstrates that a unique insert at the end of the motor repositions its lever arm and is at least in part responsible for the reversal of directionality. However, it has been proposed that there must be additional modifications within the motor that contribute to its large step size and to the reversal of directionality. To ascertain the inherent directionality of the motor core, we attached the myosin V lever arm to myosin VI, with and without the unique insert. If the insert was maintained, the motor moved toward the minus end of actin filaments, but if removed, movement was redirected toward the plus end. Single-molecule studies revealed that further adaptations within the motor increase the magnitude and variability of the plus-end directed converter movements, and unexpectedly provide the source of the highly variable myosin VI step size. Thus, the unique insert is necessary and sufficient to reverse an inherently plus-end directed myosin.
Park
Hyokeun
H
Department of Chemistry, Center for Biophysics and Computational Biology, University of Illinois, Urbana, IL 61801, USA.
Li
Anna
A
Chen
Li-Qiong
LQ
Houdusse
Anne
A
Selvin
Paul R
PR
Sweeney
H Lee
HL
D000818:Animals; D019281:Dimerization; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D013552:Swine
D020409:Molecular Motor Proteins; D011994:Recombinant Proteins; C089785:myosin VI; D018995:Myosin Heavy Chains