8B7D

Luminal domain of TMEM106B

8B7D の概要

• エントリーDOI: 10.2210/pdb8b7d/pdb
• 分子名称: Transmembrane protein 106B, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: luminal domain, fibronectin type iii (fn3), 7-bladed beta-sandwich fold, receptor binding, sars cov2, covid19, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23657.52

構造登録者

Pye, V.E.,Roustan, C.,Cherepanov, P. (登録日: 2022-09-29, 公開日: 2023-07-19, 最終更新日: 2024-11-13)

主引用文献

Baggen, J.,Jacquemyn, M.,Persoons, L.,Vanstreels, E.,Pye, V.E.,Wrobel, A.G.,Calvaresi, V.,Martin, S.R.,Roustan, C.,Cronin, N.B.,Reading, E.,Thibaut, H.J.,Vercruysse, T.,Maes, P.,De Smet, F.,Yee, A.,Nivitchanyong, T.,Roell, M.,Franco-Hernandez, N.,Rhinn, H.,Mamchak, A.A.,Ah Young-Chapon, M.,Brown, E.,Cherepanov, P.,Daelemans, D.
TMEM106B is a receptor mediating ACE2-independent SARS-CoV-2 cell entry.
Cell, 186:3427-, 2023

PubMed Abstract: SARS-CoV-2 is associated with broad tissue tropism, a characteristic often determined by the availability of entry receptors on host cells. Here, we show that TMEM106B, a lysosomal transmembrane protein, can serve as an alternative receptor for SARS-CoV-2 entry into angiotensin-converting enzyme 2 (ACE2)-negative cells. Spike substitution E484D increased TMEM106B binding, thereby enhancing TMEM106B-mediated entry. TMEM106B-specific monoclonal antibodies blocked SARS-CoV-2 infection, demonstrating a role of TMEM106B in viral entry. Using X-ray crystallography, cryogenic electron microscopy (cryo-EM), and hydrogen-deuterium exchange mass spectrometry (HDX-MS), we show that the luminal domain (LD) of TMEM106B engages the receptor-binding motif of SARS-CoV-2 spike. Finally, we show that TMEM106B promotes spike-mediated syncytium formation, suggesting a role of TMEM106B in viral fusion. Together, our findings identify an ACE2-independent SARS-CoV-2 infection mechanism that involves cooperative interactions with the receptors heparan sulfate and TMEM106B.

PubMed: 37421949
DOI: 10.1016/j.cell.2023.06.005

実験手法

X-RAY DIFFRACTION (2.59 Å)