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Structural Insights into the Lipid A Transport Pathway in MsbA

Pius S Padayatti1, Sung Chang Lee1, Robyn L Stanfield1

  • 1Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Structure (London, England : 1993)
|May 28, 2019
PubMed

Insights

The ATP-binding cassette transporter MsbA

Area of Science:

  • Structural Biology
  • Microbiology
  • Biochemistry

Background:

  • MsbA is a crucial transporter in Gram-negative bacteria, responsible for moving lipid A and lipopolysaccharide across the inner membrane.
  • Understanding MsbA's mechanism is vital for developing new antibacterial strategies.

Purpose of the Study:

  • To elucidate the structural basis of MsbA's transport mechanism.
  • To visualize the interaction of MsbA with its substrate, lipid A.

Main Methods:

  • X-ray crystallography was employed to determine the structure of MsbA.
  • Cocrystallization with lipid A and the use of a stabilizing facial amphiphile were key techniques.

Main Results:

  • The study determined the 2.8-Å resolution X-ray structure of Salmonella typhimurium MsbA in an inward-facing conformation.
  • A large opening in the transmembrane portal and putative lipid A density within the cavity and near the periplasmic surface were observed.

Conclusions:

  • The determined structure provides novel insights into the lipid A transport pathway mediated by MsbA.
  • The findings support a 'trap and flip' model for lipid A translocation across the inner membrane.
Keywords:
ABC transporterX-ray crystallographyfacial amphiphilelipid Alipid flippaselipopolysaccharide

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