9MWZ

Cryo-EM Structure of Human Enterovirus D68 USA/IL/14-18952

9MWZ の概要

• エントリーDOI: 10.2210/pdb9mwz/pdb
• 関連するPDBエントリー: 9MXC
• EMDBエントリー: 48705 48713
• 分子名称: viral protein 1, viral protein 2, viral protein 3, ... (5 entities in total)
• 機能のキーワード: virus, enterovirus
• 由来する生物種: enterovirus D68; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 89939.91

構造登録者

Xu, L.,Pintilie, G.,Varanese, L.,Carette, J.E.,Chiu, W. (登録日: 2025-01-17, 公開日: 2025-03-26, 最終更新日: 2025-06-11)

主引用文献

Varanese, L.,Xu, L.,Peters, C.E.,Pintilie, G.,Roberts, D.S.,Raj, S.,Liu, M.,Ooi, Y.S.,Diep, J.,Qiao, W.,Richards, C.M.,Callaway, J.,Bertozzi, C.R.,Jabs, S.,de Vries, E.,van Kuppeveld, F.J.M.,Nagamine, C.M.,Chiu, W.,Carette, J.E.
MFSD6 is an entry receptor for enterovirus D68.
Nature, 641:1268-1275, 2025

PubMed Abstract: With the near eradication of poliovirus due to global vaccination campaigns, attention has shifted to other enteroviruses that can cause polio-like paralysis syndrome (now termed acute flaccid myelitis (AFM)). In particular, enterovirus D68 (EV-D68) is believed to be the main driver of epidemic outbreaks of AFM in recent years, yet not much is known about EV-D68 host interactions. EV-D68 is a respiratory virus but, in rare cases, can spread to the central nervous system to cause severe neuropathogenesis. Here, we used genome-scale CRISPR screens to identify the poorly characterized multipass membrane transporter MFSD6 as a host entry factor for EV-D68. Knockout of MFSD6 expression abrogated EV-D68 infection in cell lines and primary cells corresponding to respiratory and neural cells. MFSD6 localized to the plasma membrane and was required for viral entry into host cells. MFSD6 bound directly to EV-D68 particles via its third extracellular loop (L3). We determined the cryo-EM structure of EV-D68 in complex with L3 at 2.1 Å resolution, revealing the interaction interface. A decoy receptor, engineered by fusing MFSD6(L3) to Fc, blocked EV-D68 infection of human primary lung epithelial cells, and provided near complete protection in a lethal mouse model of EV-D68 infection. Collectively, our results reveal MFSD6 as an entry receptor for EV-D68, and support targeting MFSD6 as a potential mechanism to combat infections by this emerging pathogen with pandemic potential.

PubMed: 40132641
DOI: 10.1038/s41586-025-08908-0

実験手法

ELECTRON MICROSCOPY (2 Å)