Binding of recombinant PrP c to human plasminogen: Kinetic and thermodynamic study using a resonant mirror biosensor

• Published in: Proteins, structure, function, and bioinformatics Vol. 58; no. 3; pp. 728 - 734
• Main Authors: Cuccioloni, Massimiliano, Amici, Manila, Eleuteri, Anna Maria, Biagetti, Massimo, Barocci, Simone, Angeletti, Mauro
• Format: Journal Article
• Language: English
• Published: 15-02-2005
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/prot.20346

Transmissible spongiform encephalopathies are a class of sporadic, genetic and transmissible neurodegenerative diseases that affect both humans and animals. Propagation of these diseases is thought to be due to the misfolding of a neuronal glyco‐protein, PrP
c
, into a pathological insoluble conformer, PrP
Sc
. In earlier works, some serum components were identified as exclusive PrP
Sc
‐interacting proteins (Fisher et al., Nature 2000;408:479), and thus those macromolecules were thought to represent a potential diagnostic endogenous factor discriminating between normal and pathological prion proteins. In contrast, in agreement with a recent work (Kornblatt et al., Biochem Biophys Res Commun 2003;305:518), in this paper we present a detailed thermodynamic and kinetic characterization of the interaction between recombinant bovine PrP
c 25–242
and the human serum component plasminogen, measured using a resonant mirror technique: our results reveal a high‐affinity interaction between the two binding partners. For comparison, the complex obtained from the purified full‐length PrP
c
and human plasminogen was also studied: both prion proteins (the recombinant bovine PrP
c 25–242
and the purified full‐length PrP
c
) are able to bind human plasminogen. Both kinetic and thermodynamic parameters are affected by the modulation exerted by the H
+
ions in solution. Moreover, the analysis of binding, according to canonical linkage relationships, suggests the involvement of a His residue, consistent with the interaction between other serine (pro)enzymes and their ligands. Proteins 2005. © 2004 Wiley‐Liss, Inc.