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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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Contents |
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* Residue conservation analysis
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Nat Struct Biol
17:608-613
(2010)
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PubMed id:
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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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R.Diskin,
P.M.Marcovecchio,
P.J.Bjorkman.
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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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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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J.Benckert,
N.Schmolka,
C.Kreschel,
M.J.Zoller,
A.Sturm,
B.Wiedenmann,
and
H.Wardemann
(2011).
The majority of intestinal IgA+ and IgG+ plasmablasts in the human gut are antigen-specific.
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J Clin Invest,
121,
1946-1955.
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L.T.Da,
J.M.Quan,
and
Y.D.Wu
(2011).
Understanding the binding mode and function of BMS-488043 against HIV-1 viral entry.
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Proteins,
79,
1810-1819.
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B.F.Haynes,
N.I.Nicely,
and
S.M.Alam
(2010).
HIV-1 autoreactive antibodies: are they good or bad for HIV-1 prevention?
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Nat Struct Mol Biol,
17,
543-545.
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B.Wu,
E.Y.Chien,
C.D.Mol,
G.Fenalti,
W.Liu,
V.Katritch,
R.Abagyan,
A.Brooun,
P.Wells,
F.C.Bi,
D.J.Hamel,
P.Kuhn,
T.M.Handel,
V.Cherezov,
and
R.C.Stevens
(2010).
Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists.
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Science,
330,
1066-1071.
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PDB codes:
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D.Archary,
M.L.Gordon,
T.N.Green,
H.M.Coovadia,
P.J.Goulder,
and
T.Ndung'u
(2010).
HIV-1 subtype C envelope characteristics associated with divergent rates of chronic disease progression.
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Retrovirology,
7,
92.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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