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PDBsum entry 1hfg
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Contents |
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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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Structure/function of human herpesvirus-8 mip-Ii (1-71) and the antagonist n-Terminal segment (1-10).
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Authors
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M.P.Crump,
E.Elisseeva,
J.Gong,
I.Clark-Lewis,
B.D.Sykes.
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Ref.
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FEBS Lett, 2001,
489,
171-175.
[DOI no: ]
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PubMed id
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Abstract
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Kaposi's sarcoma-associated herpesvirus encodes a chemokine called vMIP-II that
has been shown to be a broad range human chemokine receptor antagonist. Two
N-terminal peptides, vMIP-II(1-10) and vMIP-II(1-11)dimer (dimerised through
Cys11) were synthesised. Both peptides are shown to bind the CXC chemokine
receptor 4 (CXCR4). vMIP-II(1-10) was 1400-fold less potent than the native
protein whilst the vMIP-II(1-11)dimer was only 180-fold less potent. In
addition, both peptides are CXCR4 antagonists. Through analysis of non-standard,
long mixing time two-dimensional nuclear Overhauser enhancement spectroscopy
experiments, 13C relaxation data and amide chemical shift temperature gradients
for the N-terminus of vMIP-II, we show that this region populates a turn-like
structure over residues 5-8, both in the presence and absence of the full
protein scaffold. This major conformation is likely to be in fast exchange with
other conformational states but it has not previously been detected in monomeric
chemokine structures. This and other studies [Elisseeva et al. (2000) J. Biol.
suggest that there may be a link between the structuring
of the short N-terminal chemokine peptides and their ability to bind their
receptor.
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Figure 1.
Fig. 1. Receptor binding of vMIP-II and SDF-1 based
N-terminal peptides and chemotaxis inhibition by
vMIP-II(1–10). A: Competition for specific binding of
^125I-SDF-1 (4 nM) to CEM cells by SDF-1 (open circle),
SDF(1–9) monomer (open triangle), SDF(1–9)dimer (closed
triangle), vMIP-II(1–10) (open square), vMIP-II(1–11)dimer
(closed square) and N-MDC (square with cross). The data for the
N-terminal peptides of IP-10, eotaxin and eotaxin-2 are not
shown. The results are representative of duplicate experiments.
B: CEM cell migration induced by concentrations of
SDF(1–9)dimer (closed circle) and the antagonist
vMIP-II(1–10) (open triangle). Data are the means of ±S.D. of
duplicate determinations from two separate experiments.
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Figure 2.
Fig. 2. Solution structure of the vMIP-II(1–10). A bundle
of 55 calculated structures is shown superimposed on the average
structure. Residues Trp5 through to Pro8 corresponding to the
region of partial structuring are annotated.
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The above figures are
reprinted
by permission from the Federation of European Biochemical Societies:
FEBS Lett
(2001,
489,
171-175)
copyright 2001.
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