5UD9

Crystal structure of 354BG18 Fab

Summary for 5UD9

• Entry DOI: 10.2210/pdb5ud9/pdb
• Descriptor: Fab heavy chain, Light chain (3 entities in total)
• Functional Keywords: hiv, antibody, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 49179.82

Authors

Scharf, L.,Bjorkman, P.J. (deposition date: 2016-12-23, release date: 2017-02-01, Last modification date: 2024-10-23)

Primary citation

Freund, N.T.,Wang, H.,Scharf, L.,Nogueira, L.,Horwitz, J.A.,Bar-On, Y.,Golijanin, J.,Sievers, S.A.,Sok, D.,Cai, H.,Cesar Lorenzi, J.C.,Halper-Stromberg, A.,Toth, I.,Piechocka-Trocha, A.,Gristick, H.B.,van Gils, M.J.,Sanders, R.W.,Wang, L.X.,Seaman, M.S.,Burton, D.R.,Gazumyan, A.,Walker, B.D.,West, A.P.,Bjorkman, P.J.,Nussenzweig, M.C.
Coexistence of potent HIV-1 broadly neutralizing antibodies and antibody-sensitive viruses in a viremic controller.
Sci Transl Med, 9:-, 2017

PubMed Abstract: Some HIV-1-infected patients develop broad and potent HIV-1 neutralizing antibodies (bNAbs) that when passively transferred to mice or macaques can treat or prevent infection. However, bNAbs typically fail to neutralize coexisting autologous viruses due to antibody-mediated selection against sensitive viral strains. We describe an HIV-1 controller expressing HLA-B57*01 and HLA-B27*05 who maintained low viral loads for 30 years after infection and developed broad and potent serologic activity against HIV-1. Neutralization was attributed to three different bNAbs targeting nonoverlapping sites on the HIV-1 envelope trimer (Env). One of the three, BG18, an antibody directed against the glycan-V3 portion of Env, is the most potent member of this class reported to date and, as revealed by crystallography and electron microscopy, recognizes HIV-1 Env in a manner that is distinct from other bNAbs in this class. Single-genome sequencing of HIV-1 from serum samples obtained over a period of 9 years showed a diverse group of circulating viruses, 88.5% (31 of 35) of which remained sensitive to at least one of the temporally coincident autologous bNAbs and the individual's serum. Thus, bNAb-sensitive strains of HIV-1 coexist with potent neutralizing antibodies that target the virus and may contribute to control in this individual. When administered as a mix, the three bNAbs controlled viremia in HIV-1-infected humanized mice. Our finding suggests that combinations of bNAbs may contribute to control of HIV-1 infection.

PubMed: 28100831
DOI: 10.1126/scitranslmed.aal2144

Experimental method

X-RAY DIFFRACTION (1.3 Å)