G146V mutation at the hinge region of actin reveals a myosin class-specific requirement of actin conformations for motility

Taro Q.P. Noguchi, Tomotaka Komori, Nobuhisa Umeki, Noriyuki Demizu, Kohji Ito, Atsuko Hikikoshi Iwane, Kiyotaka Tokuraku, Toshio Yanagida, Taro Q.P. Uyeda

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

The G146V mutation in actin is dominant lethal in yeast. G146V actin filaments bind cofilin only minimally, presumably because cofilin binding requires the large and small actin domains to twist with respect to one another around the hinge region containing Gly-146, and the mutation inhibits that twisting motion. A number of studies have suggested that force generation by myosin also requires actin filaments to undergo conformational changes. This prompted us to examine the effects of the G146V mutation on myosin motility. When compared with wild-type actin filaments, G146V filaments showed a 78% slower gliding velocity and a 70% smaller stall force on surfaces coated with skeletal heavy meromyosin. In contrast, the G146V mutation had no effect on either gliding velocity or stall force on myosin V surfaces. Kinetic analyses of actin-myosin binding and ATPase activity indicated that the weaker affinity of actin filaments for myosin heads carrying ADP, as well as reduced actinactivated ATPase activity, are the cause of the diminished motility seen with skeletal myosin. Interestingly, the G146V mutation disrupted cooperative binding of myosin II heads to actin filaments. These data suggest that myosin-induced conformational changes in the actin filaments, presumably around the hinge region, are involved in mediating the motility of skeletal myosin but not myosin V and that the specific structural requirements for the actin subunits, and thus the mechanism of motility, differ among myosin classes.

Original languageEnglish
Pages (from-to)24339-24345
Number of pages7
JournalJournal of Biological Chemistry
Volume287
Issue number29
DOIs
Publication statusPublished - 2012 Jul 13
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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