Structural Insights into the Lipid A Transport Pathway in MsbA

Pius S. Padayatti, Sung Chang Lee, Robyn L. Stanfield, Po Chao Wen, Emad Tajkhorshid, Ian A. Wilson, Qinghai Zhang

Research output: Contribution to journalArticle

Abstract

MsbA is an essential ATP-binding cassette transporter in Gram-negative bacteria that transports lipid A and lipopolysaccharide from the cytoplasmic leaflet to the periplasmic leaflet of the inner membrane. Here we report the X-ray structure of MsbA from Salmonella typhimurium at 2.8-Å resolution in an inward-facing conformation after cocrystallization with lipid A and using a stabilizing facial amphiphile. The structure displays a large amplitude opening in the transmembrane portal, which is likely required for lipid A to pass from its site of synthesis into the protein-enclosed transport pathway. Putative lipid A density is observed further inside the transmembrane cavity, consistent with a trap and flip model. Additional electron density attributed to lipid A is observed near an outer surface cleft at the periplasmic ends of the transmembrane helices. These findings provide new structural insights into the lipid A transport pathway through comparative analysis with existing MsbA structures.

Original languageEnglish (US)
Pages (from-to)1114-1123.e3
JournalStructure
Volume27
Issue number7
DOIs
StatePublished - Jul 2 2019

Keywords

  • ABC transporter
  • X-ray crystallography
  • facial amphiphile
  • lipid A
  • lipid flippase
  • lipopolysaccharide

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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  • Cite this

    Padayatti, P. S., Lee, S. C., Stanfield, R. L., Wen, P. C., Tajkhorshid, E., Wilson, I. A., & Zhang, Q. (2019). Structural Insights into the Lipid A Transport Pathway in MsbA. Structure, 27(7), 1114-1123.e3. https://doi.org/10.1016/j.str.2019.04.007