A chimeric MIP-1alpha/RANTES protein demonstrates the use of different regions of the RANTES protein to bind and activate its receptors

J Leukoc Biol. 2001 Jun;69(6):977-85.


Human RANTES (CCL5) and MIP-1alpha (CCL3) bind and activate several CC chemokine receptors. RANTES is a high-affinity ligand for CCR1 and CCR5, and it binds CCR3 with moderate affinity and CCR4 with low affinity. MIP-1alpha has similar binding characteristics to RANTES except that it does not bind to CCR3. Here we have generated a chimera of human MIP-1alpha and RANTES, called MIP/RANTES, consisting of the eight amino terminal residues of MIP-1alpha preceding the CC motif, and the remainder of the sequence is RANTES. The chimera is able to induce chemotaxis of human monocytes. MIP/RANTES has >100-fold reduction in binding to CCR1 and does not bind to CCR3 but retains full, functional binding to CCR5. It has equivalent affinity for CCR5 to MIP-1alpha and RANTES, binding with an IC(50) of 1.12 nM, and is able to mobilize calcium and induce endocytosis of CCR5 in PBMC in a manner equi-potent to RANTES. It also retains the ability to inhibit R5 using HIV-1 strains. Therefore, we conclude that the amino terminus of RANTES is not involved in CCR5 binding, but it is essential for CCR1 and CCR3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding, Competitive
  • Calcium Signaling / drug effects
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5 / analogs & derivatives
  • Chemokine CCL5 / chemistry
  • Chemokine CCL5 / metabolism*
  • Chemotaxis / drug effects
  • Down-Regulation / drug effects
  • HIV-1 / physiology
  • Macrophage Inflammatory Proteins / chemistry
  • Macrophage Inflammatory Proteins / metabolism*
  • Molecular Sequence Data
  • Monocytes / drug effects
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptors, CCR1
  • Receptors, CCR4
  • Receptors, CCR5 / metabolism*
  • Receptors, Chemokine / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / physiology
  • Sequence Alignment
  • Sequence Homology, Amino Acid


  • CCR1 protein, human
  • CCR4 protein, human
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Macrophage Inflammatory Proteins
  • RANTES, Met-
  • Receptors, CCR1
  • Receptors, CCR4
  • Receptors, CCR5
  • Receptors, Chemokine
  • Recombinant Fusion Proteins
  • aminooxypentane-RANTES