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Nucleotide‐dependence of G‐actin conformation from multiple molecular dynamics simulations and observation of a putatively polymerization‐competent superclosed state
Author(s) -
Splettstoesser Thomas,
Noé Frank,
Oda Toshiro,
Smith Jeremy C.
Publication year - 2009
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22350
Subject(s) - polymerization , actin , nucleotide , molecular dynamics , dynamics (music) , chemistry , state (computer science) , biophysics , biology , polymer , computational chemistry , physics , biochemistry , gene , computer science , organic chemistry , algorithm , acoustics
The assembly of monomeric G‐actin into filamentous F‐actin is nucleotide dependent: ATP‐G‐actin is favored for filament growth at the “barbed end” of F‐actin, whereas ADP‐G‐actin tends to dissociate from the “pointed end.” Structural differences between ATP‐ and ADP‐G‐actin are examined here using multiple molecular dynamics simulations. The “open” and “closed” conformational states of G‐actin in aqueous solution are characterized, with either ATP or ADP in the nucleotide binding pocket. With both ATP and ADP bound, the open state closes in the absence of actin‐bound profilin. The position of the nucleotide in the protein is found to be correlated with the degree of opening of the active site cleft. Further, the simulations reveal the existence of a structurally well‐defined, compact, “superclosed” state of ATP‐G‐actin, as yet unseen crystallographically and absent in the ADP‐G‐actin simulations. The superclosed state resembles structurally the actin monomer in filament models derived from fiber diffraction and is putatively the polymerization competent conformation of ATP‐G‐actin. Proteins 2009. © 2008 Wiley‐Liss, Inc.