View source for 7fdk


==SARS-COV-2 Spike RBDMACSp36 binding to mACE2==
<StructureSection load='7fdk' size='340' side='right'caption='[[7fdk]], [[Resolution|resolution]] 3.69&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7fdk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7FDK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FDK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.69&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=7fdk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fdk OCA], [https://pdbe.org/7fdk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fdk RCSB], [https://www.ebi.ac.uk/pdbsum/7fdk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fdk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ACE2_MOUSE ACE2_MOUSE] Essential counter-regulatory carboxypeptidase of the renin-angiotensin hormone system that is a critical regulator of blood volume, systemic vascular resistance, and thus cardiovascular homeostasis. Converts angiotensin I to angiotensin 1-9, a nine-amino acid peptide with anti-hypertrophic effects in cardiomyocytes, and angiotensin II to angiotensin 1-7, which then acts as a beneficial vasodilator and anti-proliferation agent, counterbalancing the actions of the vasoconstrictor angiotensin II. Also removes the C-terminal residue from three other vasoactive peptides, neurotensin, kinetensin, and des-Arg bradykinin, but is not active on bradykinin. Also cleaves other biological peptides, such as apelins, casomorphins and dynorphin A (By similarity). By cleavage of angiotensin II, may be an important regulator of heart function (PubMed:12075344, PubMed:12967627). By cleavage of angiotensin II, may also have a protective role in acute lung injury (PubMed:16001071). Plays an important role in amino acid transport by acting as binding partner of amino acid transporter SLC6A19, regulating its trafficking on the cell surface and its activity (PubMed:18424768, PubMed:19185582, PubMed:22677001).[UniProtKB:Q9BYF1]<ref>PMID:12075344</ref> <ref>PMID:12967627</ref> <ref>PMID:16001071</ref> <ref>PMID:18424768</ref> <ref>PMID:19185582</ref> <ref>PMID:22677001</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
There is an urgent need for animal models to study SARS-CoV-2 pathogenicity. Here, we generate and characterize a novel mouse-adapted SARS-CoV-2 strain, MASCp36, that causes severe respiratory symptoms, and mortality. Our model exhibits age- and gender-related mortality akin to severe COVID-19. Deep sequencing identified three amino acid substitutions, N501Y, Q493H, and K417N, at the receptor binding domain (RBD) of MASCp36, during in vivo passaging. All three RBD mutations significantly enhance binding affinity to its endogenous receptor, ACE2. Cryo-electron microscopy analysis of human ACE2 (hACE2), or mouse ACE2 (mACE2), in complex with the RBD of MASCp36, at 3.1 to 3.7 A resolution, reveals the molecular basis for the receptor-binding switch. N501Y and Q493H enhance the binding affinity to hACE2, whereas triple mutations at N501Y/Q493H/K417N decrease affinity and reduce infectivity of MASCp36. Our study provides a platform for studying SARS-CoV-2 pathogenesis, and unveils the molecular mechanism for its rapid adaptation and evolution.

Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2.,Sun S, Gu H, Cao L, Chen Q, Ye Q, Yang G, Li RT, Fan H, Deng YQ, Song X, Qi Y, Li M, Lan J, Feng R, Guo Y, Zhu N, Qin S, Wang L, Zhang YF, Zhou C, Zhao L, Chen Y, Shen M, Cui Y, Yang X, Wang X, Tan W, Wang H, Wang X, Qin CF Nat Commun. 2021 Sep 27;12(1):5654. doi: 10.1038/s41467-021-25903-x. PMID:34580297<ref>PMID:34580297</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7fdk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Angiotensin-Converting Enzyme 3D structures|Angiotensin-Converting Enzyme 3D structures]]
*[[Spike protein 3D structures|Spike protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Cao L]]
[[Category: Wang X]]