Sequence-specific intramembrane proteolysis: identification of a recognition motif in rhomboid substrates.
Sequence-specific intramembrane proteolysis: identification of a recognition motif in rhomboid substrates.
复制标题
DOI：
10.1016/j.molcel.2009.11.006
复制
发表时间：
2009-12-25
期刊：
影响因子：
16
通讯作者：
Freeman M
中科院分区：
文献类型：
--
作者：
Strisovsky K;Sharpe HJ;Freeman M
膜内蛋白酶的广泛菱形家族的成员裂解跨膜结构域（TMD）蛋白，以调节像EGF受体信号传导，线粒体动力学和apicomplexan寄生虫的侵袭一样多样化的过程。但是，缺乏有关其底物的信息意味着大多数菱形的生物学作用仍然晦涩难懂。了解菱形如何识别其底物将阐明其机制，还可以允许底物预测。先前的工作表明，菱形底物是通过其TMD中的螺旋不稳定性指定的。在这里，我们证明菱形主要识别围绕裂解位点的特定序列。该识别基序对于底物裂解是必需的，它决定了裂解位点，并且比TM螺旋螺旋 - 涂抹残基更严格。我们的工作表明，膜内蛋白酶可以特定于序列，并且基于其识别基序的全基因组底物预测是可行的。
Members of the widespread rhomboid family of intramembrane proteases cleave transmembrane domain (TMD) proteins to regulate processes as diverse as EGF receptor signaling, mitochondrial dynamics, and invasion by apicomplexan parasites. However, lack of information about their substrates means that the biological role of most rhomboids remains obscure. Knowledge of how rhomboids recognize their substrates would illuminate their mechanism and might also allow substrate prediction. Previous work has suggested that rhomboid substrates are specified by helical instability in their TMD. Here we demonstrate that rhomboids instead primarily recognize a specific sequence surrounding the cleavage site. This recognition motif is necessary for substrate cleavage, it determines the cleavage site, and it is more strictly required than TM helix-destabilizing residues. Our work demonstrates that intramembrane proteases can be sequence specific and that genome-wide substrate prediction based on their recognition motifs is feasible.
登录
查看更多内容
影响因子：
6.7
作者：
Baker RP;Wijetilaka R;Urban S
通讯作者：
Urban S
影响因子：
11.4
作者：
Lemberg, MK;Menendez, J;Freeman, M
通讯作者：
Freeman, M
影响因子：
12.4
作者：
Jeyaraju, D. V.;Cisbani, G.;De Brito, O. M.;Koonin, E. V.;Pellegrini, L.
通讯作者：
Pellegrini, L.
影响因子：
3.6
作者：
Maegawa, Saki;Koide, Kayo;Akiyama, Yoshinori
通讯作者：
Akiyama, Yoshinori
影响因子：
5.6
作者：
Käll, L;Krogh, A;Sonnhammer, ELL
通讯作者：
Sonnhammer, ELL