5T3X

3.9 Angstrom Crystal Structure of a Fully and Natively Glycosylated BG505 SOSIP.664 HIV-1 Env Trimer in Complex with the Broadly Neutralizing Antibodies IOMA and 10-1074.

This is a non-PDB format compatible entry.

Summary for 5T3X

• Entry DOI: 10.2210/pdb5t3x/pdb
• Related: 5T3Z
• Descriptor: Envelope glycoprotein gp160, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)]alpha-D-mannopyranose-(1-3)-[beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-[beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)]alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (23 entities in total)
• Functional Keywords: hiv, n-linked glycosylation, broadly neutralizing antibodies, 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: 189016.93

Authors

Gristick, H.B.,Bjorkman, P.J. (deposition date: 2016-08-26, release date: 2016-10-05, Last modification date: 2024-10-23)

Primary citation

Gristick, H.B.,von Boehmer, L.,West, A.P.,Schamber, M.,Gazumyan, A.,Golijanin, J.,Seaman, M.S.,Fatkenheuer, G.,Klein, F.,Nussenzweig, M.C.,Bjorkman, P.J.
Natively glycosylated HIV-1 Env structure reveals new mode for antibody recognition of the CD4-binding site.
Nat.Struct.Mol.Biol., 23:906-915, 2016

PubMed Abstract: HIV-1 vaccine design is informed by structural studies elucidating mechanisms by which broadly neutralizing antibodies (bNAbs) recognize and/or accommodate N-glycans on the trimeric envelope glycoprotein (Env). Variability in high-mannose and complex-type Env glycoforms leads to heterogeneity that usually precludes visualization of the native glycan shield. We present 3.5-Å- and 3.9-Å-resolution crystal structures of the HIV-1 Env trimer with fully processed and native glycosylation, revealing a glycan shield of high-mannose and complex-type N-glycans, which we used to define complete epitopes of two bNAbs. Env trimer was complexed with 10-1074 (against the V3-loop) and IOMA, a new CD4-binding site (CD4bs) antibody. Although IOMA derives from VH1-2*02, the germline gene of CD4bs-targeting VRC01-class bNAbs, its light chain lacks the short CDRL3 that defines VRC01-class bNAbs. Thus IOMA resembles 8ANC131-class/VH1-46-derived CD4bs bNAbs, which have normal-length CDRL3s. The existence of bNAbs that combine features of VRC01-class and 8ANC131-class antibodies has implications for immunization strategies targeting VRC01-like bNAbs.

PubMed: 27617431
DOI: 10.1038/nsmb.3291

Experimental method

X-RAY DIFFRACTION (3.9 Å)