A heparin binding motif on the pro-domain of human procathepsin L mediates zymogen destabilization and activation

Fairhead, Michael and Kelly, S.M. and van der Walle, Christopher F. (2008) A heparin binding motif on the pro-domain of human procathepsin L mediates zymogen destabilization and activation. Biochemical and Biophysical Research Communications, 366 (3). pp. 862-867. ISSN 1090-2104

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Abstract

The molecular mechanism by which heparin modulates the processing of procathepsin L in the extracellular environment is proposed. We show that heparin reduces the stability of the pro form of cathepsin L at pH 5 by binding to a putative heparin binding motif (BBXB) in the pro-domain. Mutations to this motif on procathepsin L reduce heparin binding affinity and heparin-induced destabilization; in contrast, heparin only slightly destabilizes the mature cathepsin L domain. Gel analysis further shows that heparin makes procathepsin L a much better substrate for cathepsin L. Thus, heparin enhances the rate of zymogen activation by destabilization upon binding to the BBXB motif. Determining the mechanism by which procathepsin L is activated in the extracellular matrix is important to the understanding of the role that cathepsin L plays in tumour invasion.

Creators(s): Fairhead, Michael, Kelly, S.M. and van der Walle, Christopher F.;
Item type:Article
ID code:13217
Keywords:cathepsin L, heparin, pro-domain, binding motif, cysteine protease, circular dichroism, fluorescence, pharmacology, Therapeutics. Pharmacology, Pharmacy and materia medica, Microbiology, Biochemistry, Cell Biology, Molecular Biology, Biophysics
Subjects:Medicine > Therapeutics. Pharmacology
Medicine > Pharmacy and materia medica
Science > Microbiology
Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Faculty of Science > Physics > Institute of Photonics
Depositing user: Ms Ann Barker-Myles
Date deposited:13 Oct 2009 09:50
Last modified:20 Jan 2021 18:00
URI:https://strathprints.strath.ac.uk/id/eprint/13217
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