8QED

S. cerevisia Niemann-Pick type C protein NCR1 in LMNG at pH 5.5

8QED の概要

• エントリーDOI: 10.2210/pdb8qed/pdb
• 関連するPDBエントリー: 8QEB 8QEC 8QEE
• EMDBエントリー: 18350 18351 18352 18353
• 分子名称: NPC intracellular sterol transporter 1-related protein 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ERGOSTEROL, ... (4 entities in total)
• 機能のキーワード: sterol transport, vacuole, lysosome, lipid transport, membrane protein
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 135980.03

構造登録者

Frain, K.M.,Nel, L.,Dedic, E.,Olesen, E.,Stokes, D.,Panyella Pedersen, B. (登録日: 2023-08-31, 公開日: 2023-10-18, 最終更新日: 2024-11-06)

主引用文献

Frain, K.M.,Dedic, E.,Nel, L.,Bohush, A.,Olesen, E.,Thaysen, K.,Wustner, D.,Stokes, D.L.,Pedersen, B.P.
Conformational changes in the Niemann-Pick type C1 protein NCR1 drive sterol translocation.
Proc.Natl.Acad.Sci.USA, 121:e2315575121-e2315575121, 2024

PubMed Abstract: The membrane protein Niemann-Pick type C1 (NPC1, named NCR1 in yeast) is central to sterol homeostasis in eukaryotes. NCR1 is localized to the vacuolar membrane, where it is suggested to carry sterols across the protective glycocalyx and deposit them into the vacuolar membrane. However, documentation of a vacuolar glycocalyx in fungi is lacking, and the mechanism for sterol translocation has remained unclear. Here, we provide evidence supporting the presence of a glycocalyx in isolated vacuoles and report four cryo-EM structures of NCR1 in two distinct conformations, named tense and relaxed. These two conformations illustrate the movement of sterols through a tunnel formed by the luminal domains, thus bypassing the barrier presented by the glycocalyx. Based on these structures and on comparison with other members of the Resistance-Nodulation-Division (RND) superfamily, we propose a transport model that links changes in the luminal domains with a cycle of protonation and deprotonation within the transmembrane region of the protein. Our model suggests that NPC proteins work by a generalized RND mechanism where the proton motive force drives conformational changes in the transmembrane domains that are allosterically coupled to luminal/extracellular domains to promote sterol transport.

PubMed: 38568972
DOI: 10.1073/pnas.2315575121

実験手法

ELECTRON MICROSCOPY (3.27 Å)