5T3S

HIV gp140 trimer MD39-10MUTA in complex with Fabs PGT124 and 35022

Summary for 5T3S

• Entry DOI: 10.2210/pdb5t3s/pdb
• 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-(1-6)-[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, ... (13 entities in total)
• Functional Keywords: hiv-1 neutralizing antibody, immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 6
• Total formula weight: 178750.85

Authors

Stanfield, R.L.,Wilson, I.A. (deposition date: 2016-08-26, release date: 2016-09-28, Last modification date: 2024-10-23)

Primary citation

Steichen, J.M.,Kulp, D.W.,Tokatlian, T.,Escolano, A.,Dosenovic, P.,Stanfield, R.L.,McCoy, L.E.,Ozorowski, G.,Hu, X.,Kalyuzhniy, O.,Briney, B.,Schiffner, T.,Garces, F.,Freund, N.T.,Gitlin, A.D.,Menis, S.,Georgeson, E.,Kubitz, M.,Adachi, Y.,Jones, M.,Mutafyan, A.A.,Yun, D.S.,Mayer, C.T.,Ward, A.B.,Burton, D.R.,Wilson, I.A.,Irvine, D.J.,Nussenzweig, M.C.,Schief, W.R.
HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies.
Immunity, 45:483-496, 2016

PubMed Abstract: Broadly neutralizing antibodies (bnAbs) against the N332 supersite of the HIV envelope (Env) trimer are the most common bnAbs induced during infection, making them promising leads for vaccine design. Wild-type Env glycoproteins lack detectable affinity for supersite-bnAb germline precursors and are therefore unsuitable immunogens to prime supersite-bnAb responses. We employed mammalian cell surface display to design stabilized Env trimers with affinity for germline-reverted precursors of PGT121-class supersite bnAbs. The trimers maintained native-like antigenicity and structure, activated PGT121 inferred-germline B cells ex vivo when multimerized on liposomes, and primed PGT121-like responses in PGT121 inferred-germline knockin mice. Design intermediates have levels of epitope modification between wild-type and germline-targeting trimers; their mutation gradient suggests sequential immunization to induce bnAbs, in which the germline-targeting prime is followed by progressively less-mutated design intermediates and, lastly, with native trimers. The vaccine design strategies described could be utilized to target other epitopes on HIV or other pathogens.

PubMed: 27617678
DOI: 10.1016/j.immuni.2016.08.016

Experimental method

X-RAY DIFFRACTION (4.5 Å)