2GHV

Crystal structure of SARS spike protein receptor binding domain

Summary for 2GHV

• Entry DOI: 10.2210/pdb2ghv/pdb
• Related: 2ajf 2ghw
• Descriptor: Spike glycoprotein (2 entities in total)
• Functional Keywords: sars, s protein, viral protein
• Biological source: SARS coronavirus
• Cellular location: Virion membrane; Single-pass type I membrane protein: P59594
• Total number of polymer chains: 2
• Total formula weight: 45767.66

Authors

Hwang, W.C.,Lin, Y.,Santelli, E.,Sui, J.,Jaroszewski, L.,Stec, B.,Farzan, M.,Marasco, W.A.,Liddington, R.C. (deposition date: 2006-03-27, release date: 2006-09-19, Last modification date: 2024-11-20)

Primary citation

Hwang, W.C.,Lin, Y.,Santelli, E.,Sui, J.,Jaroszewski, L.,Stec, B.,Farzan, M.,Marasco, W.A.,Liddington, R.C.
Structural basis of neutralization by a human anti-severe acute respiratory syndrome spike protein antibody, 80R.
J.Biol.Chem., 281:34610-34616, 2006

PubMed Abstract: 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.

PubMed: 16954221
DOI: 10.1074/jbc.M603275200

Experimental method

X-RAY DIFFRACTION (2.2 Å)