5CEZ

Crystal Structure of the BG505 SOSIP gp140 HIV-1 Env trimer in Complex with an early putative precursor of the PGT121 family at 3.0 Angstrom

Summary for 5CEZ

• Entry DOI: 10.2210/pdb5cez/pdb
• Related: 5CEX 5CEY
• Descriptor: Envelope glycoprotein gp160, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (14 entities in total)
• Functional Keywords: hiv-1, antibody, immune system, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 6
• Total formula weight: 178725.86

Authors

Wilson, I.A.,Garces, F. (deposition date: 2015-07-08, release date: 2015-12-23, Last modification date: 2023-09-27)

Primary citation

Garces, F.,Lee, J.H.,de Val, N.,Torrents de la Pena, A.,Kong, L.,Puchades, C.,Hua, Y.,Stanfield, R.L.,Burton, D.R.,Moore, J.P.,Sanders, R.W.,Ward, A.B.,Wilson, I.A.
Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans.
Immunity, 43:1053-1063, 2015

PubMed Abstract: The high-mannose patch on the HIV-1 envelope (Env) glycoprotein is the epicenter for binding of the potent broadly neutralizing PGT121 family of antibodies, but strategies for generating such antibodies by vaccination have not been defined. We generated structures of inferred antibody intermediates by X-ray crystallography and electron microscopy to elucidate the molecular events that occurred during evolution of this family. Binding analyses revealed that affinity maturation was primarily focused on avoiding, accommodating, or binding the N137 glycan. The overall antibody approach angle to Env was defined very early in the maturation process, yet some variation evolved in the PGT121 family branches that led to differences in glycan specificities in their respective epitopes. Furthermore, we determined a crystal structure of the recombinant BG505 SOSIP.664 HIV-1 trimer with a PGT121 family member at 3.0 Å that, in concert with these antibody intermediate structures, provides insights to advance design of HIV vaccine candidates.

PubMed: 26682982
DOI: 10.1016/j.immuni.2015.11.007

Experimental method

X-RAY DIFFRACTION (3.031 Å)