2ghv

From Proteopedia

Revision as of 15:28, 15 February 2008

Crystal structure of SARS spike protein receptor binding domain

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

2GHV is a Single protein structure of sequence from Human sars coronavirus. 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

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