最温和的切割：Kex2和弗林蛋白酶的晶体结构揭示前体加工的秘密。

The kindest cuts of all: crystal structures of Kex2 and furin reveal secrets of precursor processing.

作者信息

Rockwell Nathan C, Thorner Jeremy W

机构信息

Department of Molecular and Cell Biology, Division of Biochemistry and Molecular Biology, University of California at Berkeley, Room 16, Barker Hall, Berkeley, CA 94720-3202, USA.

出版信息

Trends Biochem Sci. 2004 Feb;29(2):80-7. doi: 10.1016/j.tibs.2003.12.006.

DOI:10.1016/j.tibs.2003.12.006

PMID:15102434

Abstract

Pro-hormone or pro-protein convertases are a conserved family of eukaryotic serine proteases found in the secretory pathway. These endoproteases mature precursors for peptides and proteins that perform a wide range of physiologically important and clinically relevant functions. The first member of this family to be identified was Kex2 in the yeast Saccharomyces cerevisiae. One mammalian member of this family - furin - is responsible for processing substrates that include insulin pro-receptor, human immunodeficiency virus gp160 glycoprotein, Ebola virus glycoprotein, and anthrax protective antigen. Recent determination of the crystal structures for the catalytic core domains of both Kex2 and furin - the first for any members of this family - provide remarkable insights and a new level of understanding of substrate specificity and catalysis by the pro-protein convertases.

摘要

激素原或前体蛋白转化酶是在分泌途径中发现的一类保守的真核丝氨酸蛋白酶家族。这些内切蛋白酶使肽和蛋白质的前体成熟，这些肽和蛋白质具有广泛的生理重要功能和临床相关功能。该家族中第一个被鉴定的成员是酿酒酵母中的Kex2。该家族的一个哺乳动物成员——弗林蛋白酶——负责加工包括胰岛素原受体、人类免疫缺陷病毒gp160糖蛋白、埃博拉病毒糖蛋白和炭疽保护性抗原在内的底物。最近对Kex2和弗林蛋白酶催化核心结构域的晶体结构的测定——这是该家族任何成员的首次测定——为前体蛋白转化酶的底物特异性和催化作用提供了显著的见解和新的理解水平。