Chemical modification of a variant of human MIP-1alpha; implications for dimer structure

Protein Sci. 2000 Oct;9(10):2047-53. doi: 10.1110/ps.9.10.2047.

Abstract

A sequence variant of human MIP-1alpha, in which Asp26 has been replaced by Al alpha, has been chemically modified by the addition of 13C-labeled methyl groups at each of the lysine residues and the N-terminus. The sites of methylation have been verified by a combination of MALDI-TOF mass spectrometric experiments and tryptic digestion followed by N-terminal mapping. The effect of the modification on the structure and activity of the protein have been determined by analytical ultra-centrifugation, 13C NMR spectroscopy and receptor binding studies. The results of these experiments suggest that huMIP-alpha D26A (BB10010), when present as a dimer, adopts a globular structure, like MCP-3, rather than the elongated or cylindrical structure determined for dimers of huMIP-1beta and RANTES.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine
  • Amino Acid Substitution
  • Aspartic Acid
  • Binding Sites
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5 / chemistry
  • Dimerization
  • Genetic Variation
  • Humans
  • Macrophage Inflammatory Proteins / chemistry*
  • Macrophage Inflammatory Proteins / genetics*
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptide Fragments / chemistry
  • Protein Conformation
  • Receptors, Chemokine / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Trypsin
  • Ultracentrifugation

Substances

  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Macrophage Inflammatory Proteins
  • Peptide Fragments
  • Receptors, Chemokine
  • macrophage inflammatory protein 1alpha receptor
  • Aspartic Acid
  • Trypsin
  • Alanine