6UDK

HIV-1 bNAb 1-55 in complex with modified BG505 SOSIP-based immunogen RC1 and 10-1074

Summary for 6UDK

• Entry DOI: 10.2210/pdb6udk/pdb
• Related: 6ORN
• EMDB information: 20175 20739 20740
• Descriptor: RC1 variant of HIV-1 Env glycoprotein gp120, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)]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 broadly neutralizing antibody, bnab, env trimer, cryo-em, rc1, cd4-binding site, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1 (HIV-1); More
• Total number of polymer chains: 18
• Total formula weight: 540021.82

Authors

Abernathy, M.E.,Barnes, C.O.,Gristick, H.B.,Bjorkman, P.J. (deposition date: 2019-09-19, release date: 2020-01-29, Last modification date: 2024-10-23)

Primary citation

Schommers, P.,Gruell, H.,Abernathy, M.E.,Tran, M.K.,Dingens, A.S.,Gristick, H.B.,Barnes, C.O.,Schoofs, T.,Schlotz, M.,Vanshylla, K.,Kreer, C.,Weiland, D.,Holtick, U.,Scheid, C.,Valter, M.M.,van Gils, M.J.,Sanders, R.W.,Vehreschild, J.J.,Cornely, O.A.,Lehmann, C.,Fatkenheuer, G.,Seaman, M.S.,Bloom, J.D.,Bjorkman, P.J.,Klein, F.
Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody.
Cell, 180:471-, 2020

PubMed Abstract: Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits clinical applications. Here we describe 1-18, a new V1-46-encoded CD4 binding site (CD4bs) bNAb with outstanding breadth (97%) and potency (GeoMean IC = 0.048 μg/mL). Notably, 1-18 is not susceptible to typical CD4bs escape mutations and effectively overcomes HIV-1 resistance to other CD4bs bNAbs. Moreover, mutational antigenic profiling uncovered restricted pathways of HIV-1 escape. Of most promise for therapeutic use, even 1-18 alone fully suppressed viremia in HIV-1-infected humanized mice without selecting for resistant viral variants. A 2.5-Å cryo-EM structure of a 1-18-BG505 Env complex revealed that these characteristics are likely facilitated by a heavy-chain insertion and increased inter-protomer contacts. The ability of 1-18 to effectively restrict HIV-1 escape pathways provides a new option to successfully prevent and treat HIV-1 infection.

PubMed: 32004464
DOI: 10.1016/j.cell.2020.01.010

Experimental method

ELECTRON MICROSCOPY (3.9 Å)