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Flexibility in the ABC transporter MsbA: Alternating access with a twist

Academic Article
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Overview

related to degree

  • Roth, Christopher, Ph.D. in Biology, Scripps Research 2004 - 2008
  • Ward, Andrew, Ph.D. in Biology, Scripps Research 2003 - 2008

authors

  • Ward, Andrew
  • Reyes, C. L.
  • Yu, J.
  • Roth, Christopher
  • Chang, Geoffrey

publication date

  • November 2007

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • 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 bacterial ABC lipid flippase, MsbA, trapped in different conformations, two nucleotide-bound 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.

subject areas

  • ATP-Binding Cassette Transporters
  • Adenosine Triphosphate
  • Adenylyl Imidodiphosphate
  • Amino Acid Sequence
  • Bacterial Proteins
  • Binding Sites
  • Biological Transport, Active
  • Crystallography, X-Ray
  • Escherichia coli Proteins
  • Models, Molecular
  • Molecular Sequence Data
  • Motion
  • Protein Binding
  • Protein Conformation
  • Salmonella typhimurium
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Vibrio cholerae
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Research

keywords

  • lipid flippase
  • membrane protein structure
  • multidrug transport
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Identity

PubMed Central ID

  • PMC2141898

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0709388104

PubMed ID

  • 18024585
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Additional Document Info

start page

  • 19005

end page

  • 19010

volume

  • 104

issue

  • 48

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