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Biomolecules 2014, 4(2), 510-526; doi:10.3390/biom4020510
Article

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

1,2
, 1
 and 1,*
Received: 31 January 2014; in revised form: 2 April 2014 / Accepted: 11 April 2014 / Published: 8 May 2014
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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.
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
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

AMA 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(2):510-526.

Chicago/Turabian Style

Kojima, Aya; Konishi, Motomi; Akizawa, Toshifumi. 2014. "Prion Fragment Peptides Are Digested with Membrane Type Matrix Metalloproteinases and Acquire Enzyme Resistance through Cu2+-Binding." Biomolecules 4, no. 2: 510-526.


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