Download MendeleyStructural Insights into the Lipid A Transport Pathway in MsbA.
Padayatti, P.S., Lee, S.C., Stanfield, R.L., Wen, P.C., Tajkhorshid, E., Wilson, I.A., Zhang, Q.(2019) Structure 27: 1114
- PubMed: 31130486
- DOI: https://doi.org/10.1016/j.str.2019.04.007
- Primary Citation of Related Structures:
6BL6, 6O30 - PubMed 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.
Organizational Affiliation:
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
