Regulation of m-Calpain Activity by ¥á-Synuclein and Its C-terminal Fragment (¥á-syn61-140)

Bulletin of the Korean chemical society

Choong-Hwan Lee¹  Seung R. Paik¹  In-Hwan Lee¹  Hyun Jin Kim¹ 

关键词: ¥á-Synuclein;    Calpain;    Proteolysis;    Calpain regulator;    Parkinson¡¯s disease;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

The m-calpain activity hydrolyzing a fluorogenic substrate of N-Succinyl-Leu-Leu-Val-Tyr-7-amino-4-methylcourmarin (LLVY-AMC) was significantly stimulated by more than two-fold in the presence of 5 レM �?-synuclein at 15 ìC. The stimulation was also confirmed with azocasein. The stimulation of the peptide hydrolyzing activity required structural intactness of �?-synuclein since the C-terminally or N-terminally modified proteins such as �?-synuclein, �?-syn1-97, and �?-syn61-140 did not increase the proteolytic activity. Instead, however, the N-terminally truncated �?-syn61-140 was shown to drastically suppress the calpain activity. Since the N-terminal truncation was known to be the primary cleaving event of calpain-mediated proteolysis of �?-synuclein and the �?-syn61-140 has been demonstrated to be resistant against the calpain digestion, it has been proposed that the intracellular calpain activity could be regulated in a reciprocal manner by �?-synuclein and its proteolyzed C-terminal fragment. Based on the results, a possible physiological function of �?-synuclein has been suggested as a calpain regulator which contains both stimulatory and inhibitory activities.

【 授权许可】

Unknown