PDBsum entry 1hfg

Chemokine

PDB id: 1hfg

Contents

Protein chain

71 a.a. *

* Residue conservation analysis

PDB id:

1hfg

Name:

Chemokine

Title:

Nmr solution structure of vmip-ii 1-71 from kaposi's sarcoma- associated herpesvirus (minimized average structure).

Structure:

Viral macrophage inflammatory protein-ii. Chain: a. Fragment: residues 1-71. Synonym: vmip-ii, vmip-1b. Engineered: yes

Source:

Synthetic: yes. Human herpesvirus 8. Organism_taxid: 37296

NMR struc:

1 models

Authors:

M.P.Crump,E.Elisseeva,J.-H.Gong,I.Clark-Lewis,B.D.Sykes

Key ref:

M.P.Crump et al. (2001). Structure/function of human herpesvirus-8 MIP-II (1-71) and the antagonist N-terminal segment (1-10). FEBS Lett, 489, 171-175. PubMed id: 11165244 DOI: 10.1016/S0014-5793(00)02393-0

Date:

01-Dec-00 Release date: 07-Jan-01

Protein chain

Q98157  (VMI2_HHV8P) -  Viral macrophage inflammatory protein 2 from Human herpesvirus 8 type P (isolate GK18)

Seq: 94 a.a.

Struc: 71 a.a.

DOI no: 10.1016/S0014-5793(00)02393-0

FEBS Lett 489:171-175 (2001)

PubMed id: 11165244

Structure/function of human herpesvirus-8 MIP-II (1-71) and the antagonist N-terminal segment (1-10).

M.P.Crump, E.Elisseeva, J.Gong, I.Clark-Lewis, B.D.Sykes.

ABSTRACT

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.

Selected figure(s)

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.

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.

The above figures are reprinted by permission from the Federation of European Biochemical Societies: FEBS Lett (2001, 489, 171-175) copyright 2001.

Figures were selected by the author.