Localization of the cross-linking site of GPRVVERHK in the gamma-chain of human fibrinogen

Eur J Biochem. 1993 Dec 1;218(2):321-5. doi: 10.1111/j.1432-1033.1993.tb18380.x.

Abstract

The peptide alpha 17-24-Lys (GPRVVERHK) corresponding to the N-terminus of the alpha chain of fibrin was synthesized and used to localize its binding site in the fibrinogen molecule. The peptide was radioiodinated, incubated with fibrinogen, cross-linked with a bifunctional reagent disuccinimidyl suberate and the resulting product was analyzed in several ways, including plasmin digestion. The binding of the radioactive peptide was mainly to the gamma-chain and was inhibited by unlabelled GPRVVERHK and GPRP. After plasmin digestion, the radioactivity was present in fragment D1 and also in its gamma-chain remnant, but not in fragments D2, D3 or E3. Fragment D1 cross-linked with iodinated GPRVVERHK was purified by affinity chromatography on immobilized anti-fragment D IgG, further digested with plasmin in the presence of EGTA and the peptides were fractionated by reverse-phase HPLC. The amino acid sequence analysis of the radioactive peak revealed the presence of two peptides, gamma 357-373 and GPRVVERHK. It was concluded that the binding site for GPRVVERHK is in the sequence gamma 357-373 which is present in fragment D1 but absent in fragments D2 and D3.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Chromatography, Affinity
  • Chromatography, High Pressure Liquid
  • Cross-Linking Reagents
  • Electrophoresis, Polyacrylamide Gel
  • Fibrinogen / chemistry*
  • Humans
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism

Substances

  • Cross-Linking Reagents
  • Peptide Fragments
  • Fibrinogen