Myelin basic protein stimulates plasminogen activation via tissue plasminogen activator following binding to independent l-lysine-containing domains

Biochem Biophys Res Commun. 2017 Aug 26;490(3):855-860. doi: 10.1016/j.bbrc.2017.06.131. Epub 2017 Jun 23.

Abstract

Myelin basic protein (MBP) is a key component of myelin, the specialized lipid membrane that encases the axons of all neurons. Both plasminogen (Pg) and tissue-type plasminogen activator (t-PA) bind to MBP with high affinity. We investigated the kinetics and mechanisms involved in this process using immobilized MBP and found that Pg activation by t-PA is significantly stimulated by MBP. This mechanism involves the binding of t-PA via a lysine-dependent mechanism to the Lys91 residue of the MBP NH2-terminal region Asp82 -Pro99, and the binding of Pg via a lysine-dependent mechanism to the Lys122 residue of the MBP COOH-terminal region Leu109-Gly126. In this context, MBP mimics fibrin and because MBP is a plasmin substrate, our results suggest direct participation of the Pg activation system on MBP physiology.

Keywords: Myelin basic protein; Plasminogen; Plasminogen receptor; Tissue plasminogen activator (tPA).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Enzyme Activation
  • Humans
  • Kinetics
  • Lysine / analysis
  • Lysine / metabolism
  • Myelin Basic Protein / chemistry
  • Myelin Basic Protein / metabolism*
  • Plasminogen / metabolism*
  • Protein Binding
  • Protein Domains
  • Proteolysis
  • Tissue Plasminogen Activator / metabolism*

Substances

  • Myelin Basic Protein
  • Plasminogen
  • PLAT protein, human
  • Tissue Plasminogen Activator
  • Lysine