7E0B

The crystal structure of sorting nexin 27 and PBM complex

Summary for 7E0B

• Entry DOI: 10.2210/pdb7e0b/pdb
• Descriptor: Sorting nexin-27, PBM (3 entities in total)
• Functional Keywords: sorting nexin 27, cytosolic protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 11035.45

Authors

Shang, G.J.,Qi, J.X. (deposition date: 2021-01-27, release date: 2022-02-02, Last modification date: 2023-11-29)

Primary citation

Yang, B.,Jia, Y.,Meng, Y.,Xue, Y.,Liu, K.,Li, Y.,Liu, S.,Li, X.,Cui, K.,Shang, L.,Cheng, T.,Zhang, Z.,Hou, Y.,Yang, X.,Yan, H.,Duan, L.,Tong, Z.,Wu, C.,Liu, Z.,Gao, S.,Zhuo, S.,Huang, W.,Gao, G.F.,Qi, J.,Shang, G.
SNX27 suppresses SARS-CoV-2 infection by inhibiting viral lysosome/late endosome entry.
Proc.Natl.Acad.Sci.USA, 119:-, 2022

PubMed Abstract: After binding to its cell surface receptor angiotensin converting enzyme 2 (ACE2), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the host cell through directly fusing with plasma membrane (cell surface pathway) or undergoing endocytosis traveling to lysosome/late endosome for membrane fusion (endocytic pathway). However, the endocytic entry regulation by host cell remains elusive. Recent studies show ACE2 possesses a type I PDZ binding motif (PBM) through which it could interact with a PDZ domain-containing protein such as sorting nexin 27 (SNX27). In this study, we determined the ACE2-PBM/SNX27-PDZ complex structure, and, through a series of functional analyses, we found SNX27 plays an important role in regulating the homeostasis of ACE2 receptor. More importantly, we demonstrated SNX27, together with retromer complex (the core component of the endosomal protein sorting machinery), prevents ACE2/virus complex from entering lysosome/late endosome, resulting in decreased viral entry in cells where the endocytic pathway dominates. The ACE2/virus retrieval mediated by SNX27-retromer could be considered as a countermeasure against invasion of ACE2 receptor-using SARS coronaviruses.

PubMed: 35022217
DOI: 10.1073/pnas.2117576119

Experimental method

X-RAY DIFFRACTION (1.29 Å)