5UY3

Crystal structure of human Fab PGT144, a broadly reactive and potent HIV-1 neutralizing antibody

Summary for 5UY3

• Entry DOI: 10.2210/pdb5uy3/pdb
• Related: 3U1S 4RQQ
• Descriptor: Antibody PGT144 Fab light chain, Antibody PGT144 Fab heavy chain (2 entities in total)
• Functional Keywords: antibody, hiv env glycoprotein, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 98870.10

Authors

Julien, J.-P.,Lee, J.H.,Wilson, I.A. (deposition date: 2017-02-23, release date: 2017-04-19, Last modification date: 2024-11-20)

Primary citation

Lee, J.H.,Andrabi, R.,Su, C.Y.,Yasmeen, A.,Julien, J.P.,Kong, L.,Wu, N.C.,McBride, R.,Sok, D.,Pauthner, M.,Cottrell, C.A.,Nieusma, T.,Blattner, C.,Paulson, J.C.,Klasse, P.J.,Wilson, I.A.,Burton, D.R.,Ward, A.B.
A Broadly Neutralizing Antibody Targets the Dynamic HIV Envelope Trimer Apex via a Long, Rigidified, and Anionic beta-Hairpin Structure.
Immunity, 46:690-702, 2017

PubMed Abstract: Broadly neutralizing antibodies (bnAbs) to HIV delineate vaccine targets and are prophylactic and therapeutic agents. Some of the most potent bnAbs target a quaternary epitope at the apex of the surface HIV envelope (Env) trimer. Using cryo-electron microscopy, we solved the atomic structure of an apex bnAb, PGT145, in complex with Env. We showed that the long anionic HCDR3 of PGT145 penetrated between glycans at the trimer 3-fold axis, to contact peptide residues from all three Env protomers, and thus explains its highly trimer-specific nature. Somatic hypermutation in the other CDRs of PGT145 were crucially involved in stabilizing the structure of the HCDR3, similar to bovine antibodies, to aid in recognition of a cluster of conserved basic residues hypothesized to facilitate trimer disassembly during viral entry. Overall, the findings exemplify the creative solutions that the human immune system can evolve to recognize a conserved motif buried under a canopy of glycans.

PubMed: 28423342
DOI: 10.1016/j.immuni.2017.03.017

Experimental method

X-RAY DIFFRACTION (2.9 Å)