6vw1

From Proteopedia

(Difference between revisions)

Revision as of 07:38, 27 May 2020

Structure of SARS-CoV-2 chimeric receptor-binding domain complexed with its receptor human ACE2

6vw1, resolution 2.68Å

Structural highlights

6vw1 is a 4 chain structure with sequence from Cvhsa and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	ACE2, UNQ868/PRO1885 (HUMAN), S, 2 (CVHSA)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ACE2_HUMAN] Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.^[1] ^[2] ^[3] [SPIKE_CVHSA] S1 attaches the virion to the cell membrane by interacting with human ACE2 and CLEC4M/DC-SIGNR, initiating the infection. Binding to the receptor and internalization of the virus into the endosomes of the host cell probably induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes. S2 is a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.

Publication Abstract from PubMed

A novel SARS-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans(1,2). A key to tackling this epidemic is to understand the virus's receptor recognition mechanism, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor - human ACE2 (hACE2)(3,4). Here we determined the crystal structure of the SARS-CoV-2 receptor-binding domain (RBD) (engineered to facilitate crystallization) in complex with hACE2. Compared with the SARS-CoV RBD, a hACE2-binding ridge in SARS-CoV-2 RBD takes a more compact conformation; moreover, several residue changes in SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD/hACE2 interface. These structural features of SARS-CoV-2 RBD enhance its hACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus closely related to SARS-CoV-2, also uses hACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in hACE2 recognition shed light on potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies targeting receptor recognition by SARS-CoV-2.

Structural basis of receptor recognition by SARS-CoV-2.,Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H, Geng Q, Auerbach A, Li F Nature. 2020 Mar 30. pii: 10.1038/s41586-020-2179-y. doi:, 10.1038/s41586-020-2179-y. PMID:32225175^[4]

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

References

↑ Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000 Sep 1;87(5):E1-9. PMID:10969042
↑ Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000 Oct 27;275(43):33238-43. PMID:10924499 doi:http://dx.doi.org/10.1074/jbc.M002615200
↑ Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003 Nov 27;426(6965):450-4. PMID:14647384 doi:http://dx.doi.org/10.1038/nature02145
↑ Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H, Geng Q, Auerbach A, Li F. Structural basis of receptor recognition by SARS-CoV-2. Nature. 2020 Mar 30. pii: 10.1038/s41586-020-2179-y. doi:, 10.1038/s41586-020-2179-y. PMID:32225175 doi:http://dx.doi.org/10.1038/s41586-020-2179-y

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6vw1"

@@ Line 3: / Line 3: @@
 <SX load='6vw1' size='340' side='right' viewer='molstar' caption='[[6vw1]], [[Resolution|resolution]] 2.68&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6vw1]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Wcpv Wcpv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VW1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VW1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6vw1]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvhsa Cvhsa] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VW1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VW1 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACE2, UNQ868/PRO1885 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), S, 2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 WCPV])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACE2, UNQ868/PRO1885 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), S, 2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=694009 CVHSA])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vw1 OCA], [http://pdbe.org/6vw1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vw1 RCSB], [http://www.ebi.ac.uk/pdbsum/6vw1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vw1 ProSAT]</span></td></tr>
 </table>
@@ Line 23: / Line 23: @@
 __TOC__
 </SX>
+[[Category: Cvhsa]]
 [[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Wcpv]]
 [[Category: Aihara, H]]
 [[Category: Li, F]]

6vw1

From Proteopedia

Revision as of 07:38, 27 May 2020

Structure of SARS-CoV-2 chimeric receptor-binding domain complexed with its receptor human ACE2

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox