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

Kaposi's sarcoma-associated herpesvirus encodes a chemokine called vMIP-II that has been shown to he 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 ch emokine receptor 4 (CXCR4). VMIP-II(1-10) was 1400-fold less potent than th e native protein whilst the vMIP-II(1-11)dimer was only 180-fold less poten t. In addition, both peptides are CXCR4 antagonists, Through analysis of no nstandard, long mixing time two-dimensional nuclear Overhauser enhancement spectroscopy experiments, C-13 relaxation data and amide chemical shift tem perature 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 previo usly been detected in monomeric chemokine structures. This and other studie s [Elisseeva et al. (2000) J. Biol. Chem. 275, 26799-26805] suggest that th ere may he a link between the structuring of the short N-terminal chemokine peptides and their ability to bind their receptor. (C) 2001 Federation of European Biochemical Societies, Published by Elsevier Science B.V. All righ ts reserved.