7e0b

The crystal structure of sorting nexin 27 and PBM complex

spinqualitylabelsall models 7e0b, resolution 1.29Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7e0b is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.29Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SNX27_HUMAN Involved in endocytic trafficking (By similarity). In T lymphocytes, participates in endocytic recycling pathway. Recruits PSCDBP and HT4R to early endosomes (By similarity). Publication Abstract from PubMed 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. SNX27 suppresses SARS-CoV-2 infection by inhibiting viral lysosome/late endosome entry.,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 GF, Qi J, Shang G Proc Natl Acad Sci U S A. 2022 Jan 25;119(4):e2117576119. doi: , 10.1073/pnas.2117576119. PMID:35022217 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Sorting nexin 3D structures

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