Load-dependent mechanism of nonmuscle myosin 2

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 24; pp. 9994 - 9999
• Main Authors: Kovács, Mihály, Thirumurugan, Kavitha, Knight, Peter J, Sellers, James R
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 12-06-2007; National Acad Sciences
• Subjects: Actins; Actins - metabolism; Adenosine Diphosphate - metabolism; Adenosine Diphosphate - secretion; Adenosine Triphosphate - metabolism; Binding sites; Biochemistry; Biological Sciences; Biomechanical Phenomena; Fluorescence; Humans; Kinetics; Lead; Microfilaments; Models, Biological; Molecular Motor Proteins - chemistry; Molecular Motor Proteins - metabolism; Molecules; Muscular system; Myosin Subfragments - metabolism; Myosin Subfragments - ultrastructure; Nonmuscle Myosin Type IIA - chemistry; Nonmuscle Myosin Type IIA - metabolism; Nonmuscle Myosin Type IIA - ultrastructure; Nonmuscle Myosin Type IIB - chemistry; Nonmuscle Myosin Type IIB - metabolism; Nonmuscle Myosin Type IIB - ultrastructure; Nucleotides; Protein Binding; Protein isoforms; Proteins; Skeletal muscle; Smooth muscle; Thermodynamics
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0701181104

Loads on molecular motors regulate and coordinate their function. In a study that directly measures properties of internally strained myosin 2 heads bound to actin, we find that human nonmuscle myosins 2A and 2B show marked load-dependent changes in kinetics of ADP release but not in nucleotide binding. We show that the ADP release rate constant is increased 4-fold by the assisting load on one head and decreased 5-fold (for 2A) or 12-fold (for 2B) by the resisting load on the other. Thus these myosins, especially 2B, have marked mechanosensitivity of product release. By regulating the actin attachment of myosin heads, this provides a basis for energy-efficient tension maintenance without obstructing cellular contractility driven by other motors such as smooth muscle myosin. Whereas forward load accelerates the cycle of interaction with actin, resistive load increases duty ratio to favor tension maintenance by two-headed attachment.