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- Title
Functional adaptation of the switch-2 nucleotide sensor enables rapid processive translocation by myosin-5.
- Authors
Nagy, Nikolett T.; Sakamoto, Takeshi; Takács, Balázs; Gyimesi, Máté; Hazai, Eszter; Bikádi, Zsolt; Sellers, James R.; Kovács, Mihály
- Abstract
Active site loops that are conserved across superfamilies of myosins, kinesins, and G proteins play key roles in allosteric coupling of NTP hydrolysis to interaction with track filaments or effector proteins. In this study, we investigated how the class-specific natural variation in the switch-2 active site loop contributes to the motor function of the intracellular transporter myosin-5. We used single-molecule, rapid kinetic and spectroscopic experiments and semiempirical quantum chemical simulations to show mat the class-specific switch-2 structure including a tyrosine (Y439) in myosin-5 enables rapid processive translocation along actin filaments by facilitating Mg2+-dependent ADP release. Using wild-type control and Y439 point mutant myosin-5 proteins, we demonstrate mat the translocation speed precisely correlates with the kinetics of nucleotide exchange. Switch-2 variants can thus be used to fine-tune translocation speed while maintaining high processivity. The class-specific variation of switch-2 in various NTPase superfamilies indicates its general role in the kinetic tuning of Mg2+-dependent nucleotide exchange.
- Subjects
NUCLEOTIDES; CHROMOSOMAL translocation; MYOSIN; ACTOMYOSIN; NUCLEOTIDE exchange factors; SINGLE molecule detection
- Publication
FASEB Journal, 2010, Vol 24, Issue 11, p4480
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.10-163998