7e0b: Difference between revisions
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The | ==The crystal structure of sorting nexin 27 and PBM complex== | ||
<StructureSection load='7e0b' size='340' side='right'caption='[[7e0b]], [[Resolution|resolution]] 1.29Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7e0b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7E0B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E0B FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.29Å</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7e0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e0b OCA], [https://pdbe.org/7e0b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e0b RCSB], [https://www.ebi.ac.uk/pdbsum/7e0b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e0b ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/SNX27_HUMAN 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).<ref>PMID:17351151</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:35022217</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7e0b" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Sorting nexin 3D structures|Sorting nexin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Qi JX]] | |||
[[Category: Shang GJ]] | |||
Latest revision as of 19:44, 29 November 2023
The crystal structure of sorting nexin 27 and PBM complexThe crystal structure of sorting nexin 27 and PBM complex
Structural highlights
FunctionSNX27_HUMAN Involved in endocytic trafficking (By similarity). In T lymphocytes, participates in endocytic recycling pathway. Recruits PSCDBP and HT4R to early endosomes (By similarity).[1] Publication Abstract from PubMedAfter 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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