Title

A unique ATP hydrolysis mechanism of single-headed processive myosin, myosin IX

UMMS Affiliation

Department of Physiology

Date

12-13-2005

Document Type

Article

Subjects

Actins; Actomyosin; Adenosine Diphosphate; Adenosine Triphosphatases; Adenosine Triphosphate; Animals; Binding Sites; Calmodulin; DNA, Complementary; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Humans; Hydrolysis; Insects; Kinetics; Molecular Conformation; Muscle, Skeletal; Myosins; Protein Binding; Protein Structure, Tertiary; Rabbits; Recombinant Proteins; Time Factors

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Recent studies have revealed that myosin IX is a single-headed processive myosin, yet it is unclear how myosin IX can achieve the processive movement. Here we studied the mechanism of ATP hydrolysis cycle of actomyosin IXb. We found that myosin IXb has a rate-limiting ATP hydrolysis step unlike other known myosins, thus populating the prehydrolysis intermediate (M.ATP). M.ATP has a high affinity for actin, and, unlike other myosins, the dissociation of M.ATP from actin was extremely slow, thus preventing myosin from dissociating away from actin. The ADP dissociation step was 10-fold faster than the overall ATP hydrolysis cycle rate and thus not rate-limiting. We propose the following model for single-headed processive myosin. Upon the formation of the M.ATP intermediate, the tight binding of actomyosin IX at the interface is weakened. However, the head is kept in close proximity to actin due to the tethering role of loop 2/large unique insertion of myosin IX. There is enough freedom for the myosin head to find the next location of the binding site along with the actin filament before complete dissociation from the filament. After ATP hydrolysis, Pi is quickly released to form a strong actin binding form, and a power stroke takes place.

Rights and Permissions

Citation: J Biol Chem. 2006 Feb 24;281(8):4949-57. Epub 2005 Dec 7. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal Title

The Journal of biological chemistry

PubMed ID

16338935