4JHA

Crystal Structure of RSV-Neutralizing Human Antibody D25

Summary for 4JHA

• Entry DOI: 10.2210/pdb4jha/pdb
• Related: 4JHW
• Descriptor: D25 antigen-binding fragment heavy chain, D25 light chain (3 entities in total)
• Functional Keywords: immunoglobulin, ig, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 47830.49

Authors

Mclellan, J.S.,Chen, M.,Leung, S.,Graepel, K.W.,Du, X.,Yang, Y.,Zhou, T.,Baxa, U.,Yasuda, E.,Beaumont, T.,Kumar, A.,Modjarrad, K.,Zheng, Z.,Zhao, M.,Xia, N.,Kwong, P.D.,Graham, B.S. (deposition date: 2013-03-04, release date: 2013-05-01, Last modification date: 2024-10-16)

Primary citation

McLellan, J.S.,Chen, M.,Leung, S.,Graepel, K.W.,Du, X.,Yang, Y.,Zhou, T.,Baxa, U.,Yasuda, E.,Beaumont, T.,Kumar, A.,Modjarrad, K.,Zheng, Z.,Zhao, M.,Xia, N.,Kwong, P.D.,Graham, B.S.
Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody.
Science, 340:1113-1117, 2013

PubMed Abstract: The prefusion state of respiratory syncytial virus (RSV) fusion (F) glycoprotein is the target of most RSV-neutralizing activity in human sera, but its metastability has hindered characterization. To overcome this obstacle, we identified prefusion-specific antibodies that were substantially more potent than the prophylactic antibody palivizumab. The cocrystal structure for one of these antibodies, D25, in complex with the F glycoprotein revealed D25 to lock F in its prefusion state by binding to a quaternary epitope at the trimer apex. Electron microscopy showed that two other antibodies, AM22 and 5C4, also bound to the newly identified site of vulnerability, which we named antigenic site Ø. These studies should enable design of improved vaccine antigens and define new targets for passive prevention of RSV-induced disease.

PubMed: 23618766
DOI: 10.1126/science.1234914

Experimental method

X-RAY DIFFRACTION (1.6 Å)