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PDBsum entry 3lmj
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Immune system
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PDB id
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3lmj
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References listed in PDB file
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Key reference
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Title
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Structure of a clade c HIV-1 gp120 bound to cd4 and cd4-Induced antibody reveals anti-Cd4 polyreactivity.
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Authors
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R.Diskin,
P.M.Marcovecchio,
P.J.Bjorkman.
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Ref.
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Nat Struct Biol, 2010,
17,
608-613.
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PubMed id
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Abstract
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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.
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