6UM5

Cryo-EM structure of HIV-1 neutralizing antibody DH270 UCA3 in complex with CH848 10.17DT Env

Summary for 6UM5

• Entry DOI: 10.2210/pdb6um5/pdb
• EMDB information: 20817
• Descriptor: CH848 10.17 DT gp120, Envelope glycoprotein gp160, DH270 UCA3 Fab Heavy Chain, ... (9 entities in total)
• Functional Keywords: v3-glycan site, unmutated common ancestor, dh270 lineage, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 12
• Total formula weight: 371237.61

Authors

Acharya, P.,Henderson, R.C.,Saunders, K.O.,Haynes, B.F. (deposition date: 2019-10-09, release date: 2019-12-18, Last modification date: 2020-07-29)

Primary citation

Saunders, K.O.,Wiehe, K.,Tian, M.,Acharya, P.,Bradley, T.,Alam, S.M.,Go, E.P.,Scearce, R.,Sutherland, L.,Henderson, R.,Hsu, A.L.,Borgnia, M.J.,Chen, H.,Lu, X.,Wu, N.R.,Watts, B.,Jiang, C.,Easterhoff, D.,Cheng, H.L.,McGovern, K.,Waddicor, P.,Chapdelaine-Williams, A.,Eaton, A.,Zhang, J.,Rountree, W.,Verkoczy, L.,Tomai, M.,Lewis, M.G.,Desaire, H.R.,Edwards, R.J.,Cain, D.W.,Bonsignori, M.,Montefiori, D.,Alt, F.W.,Haynes, B.F.
Targeted selection of HIV-specific antibody mutations by engineering B cell maturation.
Science, 366:-, 2019

PubMed Abstract: A major goal of HIV-1 vaccine development is the design of immunogens that induce broadly neutralizing antibodies (bnAbs). However, vaccination of humans has not resulted in the induction of affinity-matured and potent HIV-1 bnAbs. To devise effective vaccine strategies, we previously determined the maturation pathway of select HIV-1 bnAbs from acute infection through neutralizing antibody development. During their evolution, bnAbs acquire an abundance of improbable amino acid substitutions as a result of nucleotide mutations at variable region sequences rarely targeted by activation-induced cytidine deaminase, the enzyme responsible for antibody mutation. A subset of improbable mutations is essential for broad neutralization activity, and their acquisition represents a key roadblock to bnAb development.

PubMed: 31806786
DOI: 10.1126/science.aay7199

Experimental method

ELECTRON MICROSCOPY (4.2 Å)