The structure of nonvertebrate actin: Implications for the ATP hydrolytic mechanism

Departments of ^*Biochemistry and ^¶Anatomy and Structural Biology, and ^**Center for Synchrotron Biosciences, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461; ^†Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202; ^‡Departments of Biochemistry and Molecular Biophysics and Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110; ^§Department of Pathology, Emory University, Atlanta, GA 30322; and ^‖Department of Biochemistry, University of Iowa College of Medicine, Iowa City, IA 52242

Edited by William N. Lipscomb, Harvard University, Cambridge, MA, and approved February 27, 2003 (received for review April 12, 2002)

Abstract

The structures of Saccharomyces cerevisiae, Dictyostelium, and Caenorhabditis elegans actin bound to gelsolin segment-1 have been solved and refined at resolutions between 1.9 and 1.75 Å. These structures reveal several features relevant to the ATP hydrolytic mechanism, including identification of the nucleophilic water and the roles of Gln-137 and His-161 in positioning and activating the catalytic water, respectively. The involvement of these residues in the catalytic mechanism is consistent with yeast genetics studies. This work highlights both structural and mechanistic similarities with the small and trimeric G proteins and restricts the types of mechanisms responsible for the considerable enhancement of ATP hydrolysis associated with actin polymerization. The conservation of functionalities involved in nucleotide binding and catalysis also provide insights into the mechanistic features of members of the family of actin-related proteins.

Footnotes

↵ ‡‡ To whom correspondence should be addressed. E-mail: almo{at}aecom.yu.edu.
This paper was submitted directly (Track II) to the PNAS office.
Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, www.rcsb.org (PDB ID codes 1YAG, 1NM1, 1NLV, 1NMD, and 1D4X).
Abbreviation:

F-actin,

filamentous actin