3LMJ

Structure of human anti HIV 21c Fab

Summary for 3LMJ

• Entry DOI: 10.2210/pdb3lmj/pdb
• Related: 3LQA
• Descriptor: Heavy chain of anti HIV Fab from human 21c antibody, Light chain of anti HIV Fab from human 21c antibody, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (4 entities in total)
• Functional Keywords: immunoglobulin, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 47671.20

Authors

Diskin, R.,Marcovecchio, P.M.,Bjorkman, P.J. (deposition date: 2010-01-30, release date: 2010-04-07, Last modification date: 2024-11-20)

Primary citation

Diskin, R.,Marcovecchio, P.M.,Bjorkman, P.J.
Structure of a clade C HIV-1 gp120 bound to CD4 and CD4-induced antibody reveals anti-CD4 polyreactivity.
Nat.Struct.Mol.Biol., 17:608-613, 2010

PubMed Abstract: Strategies to combat HIV-1 require structural knowledge of envelope proteins from viruses in HIV-1 clade C, the most rapidly spreading subtype in the world. We present a crystal structure containing a clade C gp120 envelope. The structure, a complex between gp120, the host receptor CD4 and the CD4-induced antibody 21c, reveals that the 21c epitope involves contacts with gp120, a nonself antigen, and with CD4, an autoantigen. Binding studies using wild-type and mutant CD4 show that 21c Fab binds CD4 in the absence of gp120, and that binding of 21c to clade C and HIV-2 gp120s requires the crystallographically observed 21c-CD4 interaction. Additional binding data suggest a role for the gp120 V1V2 loop in creating a high-affinity, but slow-forming, epitope for 21c after CD4 binds. These results contribute to a molecular understanding of CD4-induced antibodies and provide the first visualization to our knowledge of a potentially autoreactive antibody Fab complexed with both self and nonself antigens.

PubMed: 20357769
DOI: 10.1038/nsmb.1796

Experimental method

X-RAY DIFFRACTION (2.2 Å)