8TSP

Open, inward-facing MsbA structure (OIF1)

Summary for 8TSP

• Entry DOI: 10.2210/pdb8tsp/pdb
• EMDB information: 41596 41597 41598 41599 41600
• Descriptor: ATP-binding transport protein MsbA (1 entity in total)
• Functional Keywords: abc transporter, transport protein
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 129086.95

Authors

Yang, B.,Zhang, T.,Lyu, J.,Laganowsky, A.D.,Zhao, M. (deposition date: 2023-08-11, release date: 2024-06-19, Last modification date: 2025-05-14)

Primary citation

Zhang, T.,Lyu, J.,Yang, B.,Yun, S.D.,Scott, E.,Zhao, M.,Laganowsky, A.
Native mass spectrometry and structural studies reveal modulation of MsbA-nucleotide interactions by lipids.
Nat Commun, 15:5946-5946, 2024

PubMed Abstract: The ATP-binding cassette (ABC) transporter, MsbA, plays a pivotal role in lipopolysaccharide (LPS) biogenesis by facilitating the transport of the LPS precursor lipooligosaccharide (LOS) from the cytoplasmic to the periplasmic leaflet of the inner membrane. Despite multiple studies shedding light on MsbA, the role of lipids in modulating MsbA-nucleotide interactions remains poorly understood. Here we use native mass spectrometry (MS) to investigate and resolve nucleotide and lipid binding to MsbA, demonstrating that the transporter has a higher affinity for adenosine 5'-diphosphate (ADP). Moreover, native MS shows the LPS-precursor 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo)-lipid A (KDL) can tune the selectivity of MsbA for adenosine 5'-triphosphate (ATP) over ADP. Guided by these studies, four open, inward-facing structures of MsbA are determined that vary in their openness. We also report a 2.7 Å-resolution structure of MsbA in an open, outward-facing conformation that is not only bound to KDL at the exterior site, but with the nucleotide binding domains (NBDs) adopting a distinct nucleotide-free structure. The results obtained from this study offer valuable insight and snapshots of MsbA during the transport cycle.

PubMed: 39009687
DOI: 10.1038/s41467-024-50350-9

Experimental method

ELECTRON MICROSCOPY (3.9 Å)