A vertebrate myosin-I structure reveals unique insights into myosin mechanochemical tuning.
Myosins are molecular motors that power diverse cellular processes, such as rapid organelle transport, muscle contraction, and tension-sensitive anchoring. The structural adaptations in the motor that allow for this functional diversity are not known, due, in part, to the lack of high-resolution structures of highly tension-sensitive myosins. We determined a 2.3-Å resolution structure of apo-myosin-Ib (Myo1b), which is the most tension-sensitive myosin characterized. We identified a striking unique orientation of structural elements that position the motor's lever arm. This orientation results in a cavity between the motor and lever arm that holds a 10-residue stretch of N-terminal amino acids, a region that is divergent among myosins. Single-molecule and biochemical analyses show that the N terminus plays an important role in stabilizing the post power-stroke conformation of Myo1b and in tuning the rate of the force-sensitive transition. We propose that this region plays a general role in tuning the mechanochemical properties of myosins.
Pennsylvania Muscle Institute and Department of Physiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104.
Henry
H
Shuman
Michael J
MJ
Greenberg
Adam
A
Zwolak
Tianming
T
Lin
Charles V
CV
Sindelar
Roberto
R
Dominguez
E Michael
EM
Ostap
D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D024461:Myosin Type I / Q000737:chemistry*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D014714:Vertebrates
D024461:Myosin Type I
cryo-EM; mechanochemistry; optical tweezers; structural biology