کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1936459 | 1050691 | 2008 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: A heparin binding motif on the pro-domain of human procathepsin L mediates zymogen destabilization and activation A heparin binding motif on the pro-domain of human procathepsin L mediates zymogen destabilization and activation](/preview/png/1936459.png)
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.
Journal: Biochemical and Biophysical Research Communications - Volume 366, Issue 3, 15 February 2008, Pages 862–867