6B3D

Crystal structure of anti-HIV antibody PGT128 in complex with a bacterially derived synthetic mimetic of Man9.

Summary for 6B3D

• Entry DOI: 10.2210/pdb6b3d/pdb
• Descriptor: PGT128 Fab light chain, PGT128 Fab heavy chain, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose, ... (8 entities in total)
• Functional Keywords: antibody, glycan, mannose, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 50006.56

Authors

Murrell, S.,Wilson, I.A. (deposition date: 2017-09-21, release date: 2017-12-06, Last modification date: 2024-10-23)

Primary citation

Pantophlet, R.,Trattnig, N.,Murrell, S.,Lu, N.,Chau, D.,Rempel, C.,Wilson, I.A.,Kosma, P.
Bacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity.
Nat Commun, 8:1601-1601, 2017

PubMed Abstract: Oligomannose-type glycans are among the major targets on the gp120 component of the HIV envelope protein (Env) for broadly neutralizing antibodies (bnAbs). However, attempts to elicit oligomannose-specific nAbs by immunizing with natural or synthetic oligomannose have so far not been successful, possibly due to B cell tolerance checkpoints. Here we design and synthesize oligomannose mimetics, based on the unique chemical structure of a recently identified bacterial lipooligosaccharide, to appear foreign to the immune system. One of these mimetics is bound avidly by members of a family of oligomannose-specific bnAbs and their putative common germline precursor when presented as a glycoconjugate. The crystal structure of one of the mimetics bound to a member of this bnAb family confirms the antigenic resemblance. Lastly, immunization of human-antibody transgenic animals with a lead mimetic evokes nAbs with specificities approaching those of existing bnAbs. These results provide evidence for utilizing antigenic mimicry to elicit oligomannose-specific bnAbs to HIV-1.

PubMed: 29150603
DOI: 10.1038/s41467-017-01640-y

Experimental method

X-RAY DIFFRACTION (2.271 Å)