8UFE

Multidrug efflux pump EfpA from mycobacterium smegmatis

8UFE の概要

• エントリーDOI: 10.2210/pdb8ufe/pdb
• 関連するPDBエントリー: 8UFD 8WM5
• EMDBエントリー: 42205
• 分子名称: Integral membrane efflux protein EfpA, PHOSPHATIDYLETHANOLAMINE (2 entities in total)
• 機能のキーワード: multidrug efflux pump, efpa, mycobacterium smegmatis, transport protein
• 由来する生物種: Mycolicibacterium smegmatis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 49133.95

構造登録者

Wang, S.,Liao, M. (登録日: 2023-10-04, 公開日: 2024-09-11)

主引用文献

Wang, S.,Wang, K.,Song, K.,Lai, Z.W.,Li, P.,Li, D.,Sun, Y.,Mei, Y.,Xu, C.,Liao, M.
Structures of the Mycobacterium tuberculosis efflux pump EfpA reveal the mechanisms of transport and inhibition.
Nat Commun, 15:7710-7710, 2024

PubMed Abstract: As the first identified multidrug efflux pump in Mycobacterium tuberculosis (Mtb), EfpA is an essential protein and promising drug target. However, the functional and inhibitory mechanisms of EfpA are poorly understood. Here we report cryo-EM structures of EfpA in outward-open conformation, either bound to three endogenous lipids or the inhibitor BRD-8000.3. Three lipids inside EfpA span from the inner leaflet to the outer leaflet of the membrane. BRD-8000.3 occupies one lipid site at the level of inner membrane leaflet, competitively inhibiting lipid binding. EfpA resembles the related lysophospholipid transporter MFSD2A in both overall structure and lipid binding sites and may function as a lipid flippase. Combining AlphaFold-predicted EfpA structure, which is inward-open, we propose a complete conformational transition cycle for EfpA. Together, our results provide a structural and mechanistic foundation to comprehend EfpA function and develop EfpA-targeting anti-TB drugs.

PubMed: 39231991
DOI: 10.1038/s41467-024-51948-9

実験手法

ELECTRON MICROSCOPY (3.68 Å)