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Biophys. J. BioFAST: First Published January 20, 2006. doi:10.1529/biophysj.105.072900
© 2006 by the Biophysical Society.

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MUSCLE AND CONTRACTILITY

The open nucleotide pocket of the profilin:actin x-ray structure is unstable and closes in the absence of profilin

Todd Minehardt 1, Peter A. Kollman 2, Roger Cooke 3 and Edward Pate 4*

1 UCSF
2 University of California
3 Univ. of California - SF
4 WSU

* To whom correspondence should be addressed. E-mail: epate{at}wsu.edu.

Submitted on August 22, 2005
Revised on September 22, 2005
Accepted on 28 December 2005


  Abstract
The open nucleotide pocket conformation of actin in the profilin:actin•CaATP x-ray structure has been hypothesized to be a crucial intermediate for nucleotide exchange in the actin depolymerization / polymerization cycle. The requirement for ancillary modification of actin for crystallization leads to ambiguities in this interpretation, however. We have used molecular dynamics (MD) simulation to model the thermodynamic properties of the actin x-ray structure, outside the crystal lattice, in an aqueous environment with profilin removed. Our simulations show that the open nucleotide pocket, profilin-free structure is actually unstable, and closes. The coordination of actin to the nucleotide in the MD-derived, closed structure is virtually identical to that in the closed profilin:actin•SrATP x-ray structure. Thus there is currently no thermodynamically stable structure representing the open nucleotide pocket state of actin.

Key Words: actin, molecular dynamics, profilin, simulation




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Copyright © 2006 by the Biophysical Society.