7fdk

From Proteopedia

(Difference between revisions)

Current revision

SARS-COV-2 Spike RBDMACSp36 binding to mACE2

Structural highlights

7fdk is a 2 chain structure with sequence from Mus musculus and Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.69Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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]^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

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^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Crackower MA, Sarao R, Oudit GY, Yagil C, Kozieradzki I, Scanga SE, Oliveira-dos-Santos AJ, da Costa J, Zhang L, Pei Y, Scholey J, Ferrario CM, Manoukian AS, Chappell MC, Backx PH, Yagil Y, Penninger JM. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature. 2002 Jun 20;417(6891):822-8. PMID:12075344 doi:http://dx.doi.org/10.1038/nature00786
↑ Donoghue M, Wakimoto H, Maguire CT, Acton S, Hales P, Stagliano N, Fairchild-Huntress V, Xu J, Lorenz JN, Kadambi V, Berul CI, Breitbart RE. Heart block, ventricular tachycardia, and sudden death in ACE2 transgenic mice with downregulated connexins. J Mol Cell Cardiol. 2003 Sep;35(9):1043-53. PMID:12967627
↑ Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, Yang P, Sarao R, Wada T, Leong-Poi H, Crackower MA, Fukamizu A, Hui CC, Hein L, Uhlig S, Slutsky AS, Jiang C, Penninger JM. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005 Jul 7;436(7047):112-6. PMID:16001071 doi:http://dx.doi.org/nature03712
↑ Kowalczuk S, Broer A, Tietze N, Vanslambrouck JM, Rasko JE, Broer S. A protein complex in the brush-border membrane explains a Hartnup disorder allele. FASEB J. 2008 Aug;22(8):2880-7. doi: 10.1096/fj.08-107300. Epub 2008 Apr 18. PMID:18424768 doi:http://dx.doi.org/10.1096/fj.08-107300
↑ Camargo SM, Singer D, Makrides V, Huggel K, Pos KM, Wagner CA, Kuba K, Danilczyk U, Skovby F, Kleta R, Penninger JM, Verrey F. Tissue-specific amino acid transporter partners ACE2 and collectrin differentially interact with hartnup mutations. Gastroenterology. 2009 Mar;136(3):872-82. doi: 10.1053/j.gastro.2008.10.055. Epub, 2008 Oct 29. PMID:19185582 doi:http://dx.doi.org/10.1053/j.gastro.2008.10.055
↑ Fairweather SJ, Broer A, O'Mara ML, Broer S. Intestinal peptidases form functional complexes with the neutral amino acid transporter B(0)AT1. Biochem J. 2012 Aug 15;446(1):135-48. doi: 10.1042/BJ20120307. PMID:22677001 doi:http://dx.doi.org/10.1042/BJ20120307
↑ 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. Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2. Nat Commun. 2021 Sep 27;12(1):5654. PMID:34580297 doi:10.1038/s41467-021-25903-x

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7fdk"

Categories: Large Structures | Mus musculus | Severe acute respiratory syndrome coronavirus 2 | Cao L | Wang X

@@ Line 1: / Line 1: @@
-====
+==SARS-COV-2 Spike RBDMACSp36 binding to mACE2==
-<StructureSection load='7fdk' size='340' side='right'caption='[[7fdk]]' scene=''>
+<StructureSection load='7fdk' size='340' side='right'caption='[[7fdk]], [[Resolution|resolution]] 3.69&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
+<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='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>
+</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: Z-disk]]
+[[Category: Mus musculus]]
+[[Category: Severe acute respiratory syndrome coronavirus 2]]
+[[Category: Cao L]]
+[[Category: Wang X]]

7fdk

From Proteopedia

Current revision

SARS-COV-2 Spike RBDMACSp36 binding to mACE2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox