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PDBsum entry 3f58
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Immune system
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PDB id
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3f58
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Contents |
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215 a.a.
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228 a.a.
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11 a.a.
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Dual conformations for the HIV-1 gp120 V3 loop in complexes with different neutralizing fabs.
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Authors
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R.Stanfield,
E.Cabezas,
A.Satterthwait,
E.Stura,
A.Profy,
I.Wilson.
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Ref.
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Structure, 1999,
7,
131-142.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: The third hypervariable (V3) loop of HIV-1 gp120 has been termed the
principal neutralizing determinant (PND) of the virus and is involved in many
aspects of virus infectivity. The V3 loop is required for viral entry into the
cell via membrane fusion and is believed to interact with cell surface chemokine
receptors on T cells and macrophages. Sequence changes in V3 can affect
chemokine receptor usage, and can, therefore, modulate which types of cells are
infected. Antibodies raised against peptides with V3 sequences can neutralize
laboratory-adapted strains of the virus and inhibit syncytia formation. Fab
fragments of these neutralizing antibodies in complex with V3 loop peptides have
been studied by X-ray crystallography to determine the conformation of the V3
loop. RESULTS: We have determined three crystal structures of Fab 58.2, a
broadly neutralizing antibody, in complex with one linear and two cyclic
peptides the amino acid sequence of which comes from the MN isolate of the gp120
V3 loop. Although the peptide conformations are very similar for the linear and
cyclic forms, they differ from that seen for the identical peptide bound to a
different broadly neutralizing antibody, Fab 59.1, and for a similar peptide
bound to the MN-specific Fab 50.1. The conformational difference in the peptide
is localized around residues Gly-Pro-Gly-Arg, which are highly conserved in
different HIV-1 isolates and are predicted to adopt a type II beta turn.
CONCLUSIONS: The V3 loop can adopt at least two different conformations for the
highly conserved Gly-Pro-Gly-Arg sequence at the tip of the loop. Thus, the
HIV-1 V3 loop has some inherent conformational flexibility that may relate to
its biological function.
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Figure 2.
Figure 2. Stereoviews of the X-ray structures of the Fab
58.2–peptide complexes. (a) The Fab 58.2–Aib142 complex. The
Cα trace is shown for the light chain (cyan) and heavy chain
(blue) of the Fab. All atoms of the bound peptide are shown in
red. Every tenth Cα atom is highlighted with a sphere and some
atoms are labeled. (b) The Fab 58.2–His loop complex. (c) The
Fab 58.2–Ser loop complex. Figures were made with the program
MOLSCRIPT [74] .
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1999,
7,
131-142)
copyright 1999.
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