期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 48, 页码 19005-19010出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0709388104
关键词
lipid flippase; membrane protein structure; multidrug transport
资金
- NIGMS NIH HHS [P50 GM073197, R01 GM061905, GM073197, GM61905] Funding Source: Medline
ATP-binding cassette (ABC) transporters are integral membrane proteins that translocate a wide variety of substrates across cellular membranes and are conserved from bacteria to humans. Here we compare four x-ray structures of the bacteria ABC lipid flippase, MsbA, trapped in different conformations, two nucleoticlebound structures and two in the absence of nucleotide. Comparison of the nucleotide-free conformations of MsbA reveals a flexible hinge formed by extracellular loops 2 and 3. This hinge allows the nucleotide-binding domains to disassociate while the ATP-binding half sites remain facing each other. The binding of the nucleotide causes a packing rearrangement of the transmembrane helices and changes the accessibility of the transporter from cytoplasmic (inward) facing to extracellular (outward) facing. The inward and outward openings are mediated by two different sets of transmembrane helix interactions. Altogether, the conformational changes between these structures suggest that large ranges of motion may be required for substrate transport.
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