Structural Relationship between “Glutamic Acid” and “Lysine” Forms of Human Plasminogen and Their Interaction with the NH2‐Terminal Activation Peptide as Studied by Affinity Chromatography

Abstract

Urokinase digestion of maleinated plasminogen results in cleavage of the single peptide bond Arg‐68‐Met‐69, which is one of the bonds normally cleaved during the first step of the activation procedure. The inactive intermediate compound formed in this way was subjected to NH2‐terminal amino acid sequence analysis, which clearly demonstrates the structural relationship between the forms of plasminogen with different NH2‐terminal amino acids. It is thus shown that lysine‐78 and valine‐79 in the “glutamic acid” plasminogen actually are the NH2‐terminal amino acids in “lysine” and “valine” plasminogen respectively. The forms with glutamic acid in NH2‐terminal position are called plasminogen A, while all other forms lacking the NH2‐terminal part of the molecule and which can be activated in a single step are called plasminogen B. By affinity chromatographic studies of the NH2‐terminal activation peptide on insolubilized plasminogen B, it was demonstrated that this peptide has specific affinity for plasminogen B. It was also shown that this noncovalent interaction is broken by 6‐aminohexanoic acid in low concentration. The tryptic heptapeptide (Ala‐Phe‐Gln‐Tyr‐His‐Ser‐Lys) which occupies the positions number 45 to 51 in the NH2‐terminal activation peptide (as well as in the intact plasminogen molecule) is shown to be responsible for this interaction which seems to be of great importance for the conformational state of the plasminogen molecule. Copyright © 1975, Wiley Blackwell. All rights reserved