Solution structure of CINC/Gro investigated by heteronuclear NMR

J Biochem. 1998 Jan;123(1):62-70. doi: 10.1093/oxfordjournals.jbchem.a021917.

Abstract

Cytokine-induced neutrophil chemoattractant (CINC/Gro) is a chemotactic factor for neutrophils in the rat and a member of the CXC chemokine family. The refined three-dimensional structure of CINC/Gro was derived with the aid of heteronuclear magnetic resonance spectroscopy and a hybrid method of distance geometry and simulated annealing. The backbone atomic r.m.s. differences for 19 structures about the mean coordinates for residues 7 to 70 are 0.69+/-0.15 A for the dimer and 0.56+/-0.13 A for the monomer. The N terminal region containing an ELR sequence, an essential motif for chemotactic activity, is disordered in solution, as in other CXC chemokines. The dimer structure consists of a six-stranded anti-parallel beta sheet with two C-terminal alpha helices on the beta sheet. The overall dimer structure of CINC/Gro is similar to that of human MGSA, though the backbone r.m.s.d.s between CINC/Gro and the two MGSA structures were high (1.81 and 2.34 A for the monomer) in spite of the high sequence homology (67%). The major difference resides in the relative position of the C-terminal alpha helix with respect to the beta sheet. This results in a difference of interhelical distances in the dimer: wider (15 A) in CINC/Gro, as in IL-8, than in MGSA (11.7 and 10 A).

MeSH terms

  • Animals
  • Chemokine CXCL1
  • Chemokines / chemistry
  • Chemokines, CXC*
  • Chemotactic Factors / chemistry*
  • Growth Substances / chemistry*
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Interleukin-8 / chemistry
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Conformation
  • Rats
  • Recombinant Proteins / chemistry

Substances

  • CXCL1 protein, human
  • Chemokine CXCL1
  • Chemokines
  • Chemokines, CXC
  • Chemotactic Factors
  • Cxcl1 protein, rat
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-8
  • Recombinant Proteins