9FV7

MsbA in Amphipol A8-35 inward-facing wide (+) open

Summary for 9FV7

• Entry DOI: 10.2210/pdb9fv7/pdb
• EMDB information: 50791
• Descriptor: ATP-dependent lipid A-core flippase (1 entity in total)
• Functional Keywords: abc transporter, transport protein
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 129061.09

Authors

Hoffmann, L.,Baier, A.,Jorde, L.,Kamel, M.,Schaefer, J.,Schnelle, K.,Scholz, A.,Shvarev, D.,Wong, J.,Parey, K.,Januliene, D.,Moeller, A. (deposition date: 2024-06-26, release date: 2025-03-19)

Primary citation

Hoffmann, L.,Baier, A.,Jorde, L.,Kamel, M.,Schafer, J.H.,Schnelle, K.,Scholz, A.,Shvarev, D.,Wong, J.E.M.M.,Parey, K.,Januliene, D.,Moeller, A.
The ABC transporter MsbA in a dozen environments.
Structure, 2025

PubMed Abstract: High-resolution structure determination of membrane proteins typically requires reconstitution into artificial membrane mimics. The choice of the specific membrane substitute can strongly affect the protein's specific activity, stability, and conformational spectrum, potentially leading to errors or misinterpretation during analysis. The bacterial ATP-binding cassette transporter MsbA is a prominent example of such environment-specific bias. Here, we present a systematic analysis of the conformational spectrum of MsbA, stabilized in a dozen environments, using cryoelectron microscopy (cryo-EM), and show pronounced feedback between the membrane mimetics and the transporter. Detergents generally favor wide inward-facing conformations while nanodiscs induce narrower conformations. Notably, only in three tested environments, MsbA samples the full movement of the nucleotide-binding domains, including narrow and wide conformations. We expect this study to serve as a blueprint for other membrane proteins, even where a structural reaction to the hydrophobic environment is not directly visible but still critical for the proteins' function.

PubMed: 40056915
DOI: 10.1016/j.str.2025.02.002

Experimental method

ELECTRON MICROSCOPY (4 Å)