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2ghw
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Severe acute respiratory syndrome (SARS) is a newly emerged infectious | + | Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease that caused pandemic spread in 2003. The etiological agent of SARS is a novel coronavirus (SARS-CoV). The coronaviral surface spike protein S is a type I transmembrane glycoprotein that mediates initial host binding via the cell surface receptor angiotensin-converting enzyme 2 (ACE2), as well as the subsequent membrane fusion events required for cell entry. Here we report the crystal structure of the S1 receptor binding domain (RBD) in complex with a neutralizing antibody, 80R, at 2.3 A resolution, as well as the structure of the uncomplexed S1 RBD at 2.2 A resolution. We show that the 80R-binding epitope on the S1 RBD overlaps very closely with the ACE2-binding site, providing a rationale for the strong binding and broad neutralizing ability of the antibody. We provide a structural basis for the differential effects of certain mutations in the spike protein on 80R versus ACE2 binding, including escape mutants, which should facilitate the design of immunotherapeutics to treat a future SARS outbreak. We further show that the RBD of S1 forms dimers via an extensive interface that is disrupted in receptor- and antibody-bound crystal structures, and we propose a role for the dimer in virus stability and infectivity. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Farzan, M.]] | [[Category: Farzan, M.]] | ||
| - | [[Category: Hwang, W | + | [[Category: Hwang, W C.]] |
[[Category: Jaroszewski, L.]] | [[Category: Jaroszewski, L.]] | ||
| - | [[Category: Liddington, R | + | [[Category: Liddington, R C.]] |
[[Category: Lin, Y.]] | [[Category: Lin, Y.]] | ||
| - | [[Category: Marasco, W | + | [[Category: Marasco, W A.]] |
[[Category: Santelli, E.]] | [[Category: Santelli, E.]] | ||
[[Category: Stec, B.]] | [[Category: Stec, B.]] | ||
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[[Category: sars]] | [[Category: sars]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:31:50 2008'' |
Revision as of 15:31, 21 February 2008
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Crystal structure of SARS spike protein receptor binding domain in complex with a neutralizing antibody, 80R
Overview
Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease that caused pandemic spread in 2003. The etiological agent of SARS is a novel coronavirus (SARS-CoV). The coronaviral surface spike protein S is a type I transmembrane glycoprotein that mediates initial host binding via the cell surface receptor angiotensin-converting enzyme 2 (ACE2), as well as the subsequent membrane fusion events required for cell entry. Here we report the crystal structure of the S1 receptor binding domain (RBD) in complex with a neutralizing antibody, 80R, at 2.3 A resolution, as well as the structure of the uncomplexed S1 RBD at 2.2 A resolution. We show that the 80R-binding epitope on the S1 RBD overlaps very closely with the ACE2-binding site, providing a rationale for the strong binding and broad neutralizing ability of the antibody. We provide a structural basis for the differential effects of certain mutations in the spike protein on 80R versus ACE2 binding, including escape mutants, which should facilitate the design of immunotherapeutics to treat a future SARS outbreak. We further show that the RBD of S1 forms dimers via an extensive interface that is disrupted in receptor- and antibody-bound crystal structures, and we propose a role for the dimer in virus stability and infectivity.
About this Structure
2GHW is a Single protein structure of sequence from Homo sapiens and Human sars coronavirus with as ligand. Full crystallographic information is available from OCA.
Reference
Structural basis of neutralization by a human anti-severe acute respiratory syndrome spike protein antibody, 80R., Hwang WC, Lin Y, Santelli E, Sui J, Jaroszewski L, Stec B, Farzan M, Marasco WA, Liddington RC, J Biol Chem. 2006 Nov 10;281(45):34610-6. Epub 2006 Sep 5. PMID:16954221
Page seeded by OCA on Thu Feb 21 17:31:50 2008
