Title

Blebbistatin effects on muscle protein myosin function

Document Type

Presentation

Journal/Book Title/Conference

Undergraduate Research Symposium

Publisher

Cornerstone

Location

Mankato, MN

Publication Date

4-18-2016

Abstract

Muscle contraction and relaxation is driven by the interaction of myosin and its major binding partner actin. In this actomyosin complex, myosin is the molecular “motor” using ATP, to produce force and movement. The myosin motor domain is composed of three major parts: the force-generating domain, including relay helix, SH1 helix, and converter; the ATP binding pocket, and the actin-binding cleft. At the molecular level, myosin undergoes a series of structural changes upon force generation, including the bending of the relay helix and a large-scale rotation of the converter. During contraction, the relay helix exhibits a “straight” conformation followed by bending during relaxation. Muscle relaxation has recently shown to exist in highly-ordered relaxed state, known as the super-relaxed (SRX) state. The SRX state is characterized by slow ATP turnover and it is believed to play a role in heart diseases, particularly in hypertrophic cardiomyopathy (HCM), ischemia, and hypoxia. Recent studies have shown blebbistatin, a potent drug inhibitor of myosin, binds tightly to the myosin motor domain and mimics the SRX state. Blebbistatin is a useful tool in studying muscle SRX state mechanisms and for method development in the treatment of cardiac muscle dysfunction. This project focuses on understanding how blebbistatin and the SRX state effect myosin structural dynamics with emphasis on changes in the relay helix conformation.

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