Next Article in Journal
Structure and Function of the LmbE-like Superfamily
Previous Article in Journal
Decoding F508del Misfolding in Cystic Fibrosis
Article Menu

Export Article

Open AccessArticle
Biomolecules 2014, 4(2), 510-526; https://doi.org/10.3390/biom4020510

Prion Fragment Peptides Are Digested with Membrane Type Matrix Metalloproteinases and Acquire Enzyme Resistance through Cu2+-Binding

1
Analytical Chemistry, Pharmaceutical Science, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan
2
Division of Cellular and Molecular Biology, Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 180-8639, Japan
*
Author to whom correspondence should be addressed.
Received: 31 January 2014 / Revised: 2 April 2014 / Accepted: 11 April 2014 / Published: 8 May 2014
View Full-Text   |   Download PDF [1518 KB, uploaded 9 May 2014]   |  

Abstract

Prions are the cause of neurodegenerative disease in humans and other mammals. The structural conversion of the prion protein (PrP) from a normal cellular protein (PrPC) to a protease-resistant isoform (PrPSc) is thought to relate to Cu2+ binding to histidine residues. In this study, we focused on the membrane-type matrix metalloproteinases (MT-MMPs) such as MT1-MMP and MT3-MMP, which are expressed in the brain as PrPC-degrading proteases. We synthesized 21 prion fragment peptides. Each purified peptide was individually incubated with recombinant MT1-MMP or MT3-MMP in the presence or absence of Cu2+ and the cleavage sites determined by LC-ESI-MS analysis. Recombinant MMP-7 and human serum (HS) were also tested as control. hPrP61-90, from the octapeptide-repeat region, was cleaved by HS but not by the MMPs tested here. On the other hand, hPrP92-168 from the central region was cleaved by MT1-MMP and MT3-MMP at various sites. These cleavages were inhibited by treatment with Cu2+. The C-terminal peptides had higher resistance than the central region. The data obtained from this study suggest that MT-MMPs expressed in the brain might possess PrPC-degrading activity. View Full-Text
Keywords: prion protein; fragment peptide; MT1-MMP; MT3-MMP; MMP-7; Cu2+; degradation prion protein; fragment peptide; MT1-MMP; MT3-MMP; MMP-7; Cu2+; degradation
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Kojima, A.; Konishi, M.; Akizawa, T. Prion Fragment Peptides Are Digested with Membrane Type Matrix Metalloproteinases and Acquire Enzyme Resistance through Cu2+-Binding. Biomolecules 2014, 4, 510-526.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Biomolecules EISSN 2218-273X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top