4JPW

Crystal structure of broadly and potently neutralizing antibody 12a21 in complex with hiv-1 strain 93th057 gp120 mutant

Summary for 4JPW

• Entry DOI: 10.2210/pdb4jpw/pdb
• Related: 3NGB 3SE8 3SE9 4GW4 4JPV
• Descriptor: HIV-1 CLADE A/E STRAIN 73TH057 GP120 WITH MUTATION H375S, HEAVY CHAIN OF ANTIBODY 12A21, LIGHT CHAIN OF ANTIBODY 12A21, ... (6 entities in total)
• Functional Keywords: hiv, gp120, cd4-binding site, 12a21, neutralization, vaccine, antibody, envelope protein, viral protein-immune system complex, viral protein/immune system
• Biological source: HUMAN IMMUNODEFICIENCY VIRUS 1; More
• Total number of polymer chains: 3
• Total formula weight: 88912.82

Authors

Acharya, P.,Luongo, T.,Zhou, T.,Kwong, P.D. (deposition date: 2013-03-19, release date: 2013-04-17, Last modification date: 2023-09-20)

Primary citation

Klein, F.,Diskin, R.,Scheid, J.F.,Gaebler, C.,Mouquet, H.,Georgiev, I.S.,Pancera, M.,Zhou, T.,Incesu, R.B.,Fu, B.Z.,Gnanapragasam, P.N.,Oliveira, T.Y.,Seaman, M.S.,Kwong, P.D.,Bjorkman, P.J.,Nussenzweig, M.C.
Somatic mutations of the immunoglobulin framework are generally required for broad and potent HIV-1 neutralization.
Cell(Cambridge,Mass.), 153:126-138, 2013

PubMed Abstract: Broadly neutralizing antibodies (bNAbs) to HIV-1 can prevent infection and are therefore of great importance for HIV-1 vaccine design. Notably, bNAbs are highly somatically mutated and generated by a fraction of HIV-1-infected individuals several years after infection. Antibodies typically accumulate mutations in the complementarity determining region (CDR) loops, which usually contact the antigen. The CDR loops are scaffolded by canonical framework regions (FWRs) that are both resistant to and less tolerant of mutations. Here, we report that in contrast to most antibodies, including those with limited HIV-1 neutralizing activity, most bNAbs require somatic mutations in their FWRs. Structural and functional analyses reveal that somatic mutations in FWR residues enhance breadth and potency by providing increased flexibility and/or direct antigen contact. Thus, in bNAbs, FWRs play an essential role beyond scaffolding the CDR loops and their unusual contribution to potency and breadth should be considered in HIV-1 vaccine design.

PubMed: 23540694
DOI: 10.1016/j.cell.2013.03.018

Experimental method

X-RAY DIFFRACTION (2.904 Å)