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Opening of the ADP‐bound active site in the ABC transporter ATPase dimer: Evidence for a constant contact, alternating sites model for the catalytic cycle
Author(s) -
Jones Peter M.,
George Anthony M.
Publication year - 2008
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.22250
Subject(s) - dimer , transmembrane domain , catalytic cycle , chemistry , conformational change , nucleotide , cyclic nucleotide binding domain , atp hydrolysis , biophysics , stereochemistry , transmembrane protein , atp binding cassette transporter , protein structure , atpase , crystallography , transporter , catalysis , membrane , biochemistry , biology , enzyme , receptor , gene , organic chemistry
ABC transporters are ubiquitous, ATP‐dependent transmembrane pumps. The mechanism by which ATP hydrolysis in the nucleotide‐binding domain (NBD) effects conformational changes in the transmembrane domain that lead to allocrite translocation remains largely unknown. A possible aspect of this mechanism was suggested by previous molecular dynamics simulations of the MJ0796 NBD dimer, which revealed a novel, nucleotide‐dependent intrasubunit conformational change involving the relative rotation of the helical and catalytic subdomains. Here, we find that in four of five simulations of the ADP/ATP‐bound dimer, the relative rotation of the helical and catalytic subdomains in the ADP‐bound monomer results in opening of the ADP‐bound active site, probably sufficient or close to sufficient to allow nucleotide exchange. We also observe that in all five simulations of the ADP/ATP‐bound dimer, the intimate contact of the LSGGQ signature sequence with the ATP γ‐phosphate is weakened by the intrasubunit conformational change within the ADP‐bound monomer. We discuss how these results support a constant contact model for the function of the NBD dimer in contrast to switch models, in which the NBDs are proposed to fully disassociate during the catalytic cycle. Proteins 2009. © 2008 Wiley‐Liss, Inc.