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PDBsum entry 2b4c
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Viral protein/immune system
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PDB id
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2b4c
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Contents |
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339 a.a.
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175 a.a.
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215 a.a.
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233 a.a.
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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 V3-Containing HIV-1 gp120 core.
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Authors
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C.C.Huang,
M.Tang,
M.Y.Zhang,
S.Majeed,
E.Montabana,
R.L.Stanfield,
D.S.Dimitrov,
B.Korber,
J.Sodroski,
I.A.Wilson,
R.Wyatt,
P.D.Kwong.
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Ref.
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Science, 2005,
310,
1025-1028.
[DOI no: ]
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PubMed id
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Abstract
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The third variable region (V3) of the HIV-1 gp120 envelope glycoprotein is
immunodominant and contains features essential for coreceptor binding. We
determined the structure of V3 in the context of an HIV-1 gp120 core complexed
to the CD4 receptor and to the X5 antibody at 3.5 angstrom resolution. Binding
of gp120 to cell-surface CD4 would position V3 so that its coreceptor-binding
tip protrudes 30 angstroms from the core toward the target cell membrane. The
extended nature and antibody accessibility of V3 explain its immunodominance.
Together, the results provide a structural rationale for the role of V3 in HIV
entry and neutralization.
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Figure 1.
Fig. 1. Structure of an HIV-1 gp120 core with V3. The crystal
structure of core gp120 (gray) with an intact V3 (red) is shown
bound to the membrane-distal two domains of the CD4 receptor
(yellow) and the Fab portion of the X5 antibody (dark and light
blue). In this orientation, the viral membrane would be
positioned toward the top of the page and the target cell toward
the bottom.
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Figure 3.
Fig. 3. Modeled trimer and coreceptor schematic. (A) V3 in the
context of a trimer at the target cell surface. The structure of
the CD4-triggered gp120 with V3 was superimposed onto the
structure of four-domain CD4 (39) and the trimer model obtained
by quantification of surface parameters (32). In this
orientation, the target cell membrane and coreceptor are
expected to be positioned toward the bottom of the page. (B)
Schematic of coreceptor interaction. CCR5 (green) is shown with
its tyrosine-sulfated N terminus (at residues 3, 10, 14, and 15)
and three extracellular loops (ECLs). V3 (red) is shown with its
conserved base interacting with the sulfated CCR5 N terminus and
its flexible legs allowing its conserved V3 tip to reach the
second ECL of CCR5.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2005,
310,
1025-1028)
copyright 2005.
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