TWO MODES OF BINDING OF MYOSIN HEADS TO ACTIN FILAMENTS

  • Borejdo, Julian (PI)
  • BOREJDO, JULIAN (PI)
  • BOREJDO, JULIAN (PI)

Project Details

Description

DESCRIPTION: The applicant and his colleagues showed earlier that a
myosin head (S1) can attach either to one or to two actin protomers in
an actin filament, depending of whether filament is saturated or
unsaturated with S1's. The objective of the project is to test a
hypothesis, which was stimulated by this finding, that a major part of
a power stroke of skeletal muscle consists of orientational change
associated with transition of myosin head from a state in which it binds
one actin to a state in which it binds to two actins. In this
application they propose to the test this hypothesis by: (i) checking
whether the kinetics of binding of S1 to unsaturated filament is
consistent with 1 S1 binding to 2 actins; (ii) identifying the amino
acid residues involved in making the second contact between S1 and actin;
(iii) inducing point mutations in S1 to demonstrate the importance of the
second actin binding site; (iv) testing whether cross-bridges in rigor
muscle bind to two actins; (v) testing whether the two binding states
can be seen during hydrolysis of ATP.

The significance of this project is that it presents a critical
hypothesis about a fundamental problem in contractility and proposes to
test it experimentally. The idea of two binding states and that the
transition between them is involved in force generation will be checked
in skeletal and smooth muscle, but applies perhaps to the broader
category of motor-driven processes. Testing this idea certainly will
contribute to the understanding of the molecular changes occurring in
acto-S1 during contraction. It is likely that the elucidation of the
molecular mechanism of contraction of skeletal and smooth muscle will
lead to better modalities in treating diseased muscle.
StatusFinished
Effective start/end date1/01/9031/03/02

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