4RBP

Crystal structure of HIV neutralizing antibody 2G12 in complex with a bacterial oligosaccharide analog of mammalian oligomanose

Summary for 4RBP

• Entry DOI: 10.2210/pdb4rbp/pdb
• Related: 1OM3 1OP3 1OP5 1ZLS 1ZLU 1ZLV 1ZLW 2OQJ 3OAU 3OAY 3OAZ 3OB0
• Descriptor: Fab 2G12 light chain, Fab 2G12 heavy chain, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-5)-3-deoxy-alpha-D-manno-oct-2-ulopyranosonic acid, ... (5 entities in total)
• Functional Keywords: immunoglobulin fold, hiv neutralizing, hiv-1 gp120, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 96929.81

Authors

Stanfield, R.L.,Wilson, I.A.,De Castro, C.,Marzaioli, A.M.,Pantophlet, R. (deposition date: 2014-09-12, release date: 2014-11-26, Last modification date: 2024-11-06)

Primary citation

Stanfield, R.L.,De Castro, C.,Marzaioli, A.M.,Wilson, I.A.,Pantophlet, R.
Crystal structure of the HIV neutralizing antibody 2G12 in complex with a bacterial oligosaccharide analog of mammalian oligomannose.
Glycobiology, 25:412-419, 2015

PubMed Abstract: Human immunodeficiency virus-1 (HIV-1) is a major public health threat that continues to infect millions of people worldwide each year. A prophylactic vaccine remains the most cost-effective way of globally reducing and eliminating the spread of the virus. The HIV envelope spike, which is the target of many vaccine design efforts, is densely mantled with carbohydrate and several potent broadly neutralizing antibodies to HIV-1 recognize carbohydrate on the envelope spike as a major part of their epitope. However, immunizing with recombinant forms of the envelope glycoprotein does not typically elicit anti-carbohydrate antibodies. Thus, studies of alternative antigens that may serve as a starting point for carbohydrate-based immunogens are of interest. Here, we present the crystal structure of one such anti-carbohydrate HIV neutralizing antibody (2G12) in complex with the carbohydrate backbone of the lipooligosaccharide from Rhizobium radiobacter strain Rv3, which exhibits a chemical structure that naturally mimics the core high-mannose carbohydrate epitope of 2G12 on HIV-1 gp120. The structure described here provides molecular evidence of the structural homology between the Rv3 oligosaccharide and highly abundant carbohydrates on the surface of HIV-1 and raises the potential for the design of novel glycoconjugates that may find utility in efforts to develop immunogens for eliciting carbohydrate-specific neutralizing antibodies to HIV.

PubMed: 25380763
DOI: 10.1093/glycob/cwu123

Experimental method

X-RAY DIFFRACTION (1.85 Å)