Alternating access in maltose transporter mediated by rigid-body rotations.

Full Abstract

ATP-binding cassette transporters couple ATP hydrolysis to substrate translocation through an alternating access mechanism, but the nature of the conformational changes in a transport cycle remains elusive. Previously we reported the structure of the maltose transporter MalFGK(2) in an outward-facing conformation in which the transmembrane (TM) helices outline a substrate-binding pocket open toward the periplasmic surface and ATP is poised for hydrolysis along the closed nucleotide-binding dimer interface. Here we report the structure of the nucleotide-free maltose transporter in which the substrate binding pocket is only accessible from the cytoplasm and the nucleotide-binding interface is open. Comparison of the same transporter crystallized in two different conformations reveals that alternating access involves rigid-body rotations of the TM subdomains that are coupled to the closure and opening of the nucleotide-binding domain interface. The comparison also reveals that point mutations enabling binding protein-independent transport line dynamic interfaces in the TM region.

Author information

Author/s: Khare, Dheeraj (D); Oldham, Michael L (ML); Orelle, Cedric (C); Davidson, Amy L (AL); Chen, Jue (J);

Affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.

Grants: R01 GM049261-13 (Agency:NIGMS NIH HHS) ; R01 GM070515-05 (Agency:NIGMS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Molecular cell (Mol Cell), published in United States. (Language: eng)

Reference: 2009-Feb; vol 33 (issue 4) : pp 528-36

Dates: Created 2009/03/02; Completed 2009/04/06; Revised 2009/08/28;

PMID: 19250913, status: MEDLINE (last retrieved date: 8/31/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.