Sequence-derived structural features driving proteolytic processing.
Sequence-derived structural features driving proteolytic processing.
复制标题
DOI：
10.1002/pmic.201300416
复制
发表时间：
2014-01
期刊：
影响因子：
3.4
通讯作者：
Kazanov, Marat D.
中科院分区：
文献类型：
--
作者：
Belushkin, Alexander A.;Vinogradov, Dmitry V.;Gelfand, Mikhail S.;Osterman, Andrei L.;Cieplak, Piotr;Kazanov, Marat D.
关键词：
蛋白水解信号传导或调节蛋白水解是许多重要途径的重要组成部分，如Notch，Wnt和Hedgehog。切割的底物区域的结构如何影响蛋白水解加工的功效仍有待探索。在这里，我们使用CutDB中捕获的超过5000个实验验证的蛋白水解事件的数据集，分析了来自底物序列的各种结构特征在蛋白水解中的相对重要性。对溶剂的可及性被认为是蛋白水解加工的多肽链的基本性质。发现蛋白质水解事件几乎均匀地分布在三种类型的二级结构中，尽管在环中有一些富集。发现α-螺旋中的裂解在明显倾向于去折叠的区域相对丰富，而β-结构中的裂解倾向于位于β-折叠的外围。应用相同的统计程序的蛋白水解事件分为单独的组，根据催化类的蛋白酶证明了结果的一致性，并证实了蛋白水解的结构机制是普遍的。序列衍生的结构特征的估计预测能力，这被证明是足够高的，提出了一个基本原理，它们用于蛋白水解事件的生物信息学预测。
Proteolytic signaling, or regulated proteolysis, is an essential part of many important pathways such as Notch, Wnt, and Hedgehog. How the structure of the cleaved substrate regions influences the efficacy of proteolytic processing remains underexplored. Here, we analyzed the relative importance in proteolysis of various structural features derived from substrate sequences using a dataset of more than five thousand experimentally verified proteolytic events captured in CutDB. Accessibility to the solvent was recognized as an essential property of a proteolytically processed polypeptide chain. Proteolytic events were found nearly uniformly distributed among three types of secondary structure, although with some enrichment in loops. Cleavages in α-helices were found to be relatively abundant in regions apparently prone to unfolding, while cleavages in β-structures tended to be located at the periphery of β-sheets. Application of the same statistical procedures to proteolytic events divided into separate sets according to the catalytic classes of proteases proved consistency of the results and confirmed that the structural mechanisms of proteolysis are universal. The estimated prediction power of sequence-derived structural features, which turned out to be sufficiently high, presents a rationale for their use in bioinformatic prediction of proteolytic events.
登录
查看更多内容
影响因子：
3
作者：
Faraggi, Eshel;Zhang, Tuo;Yang, Yuedong;Kurgan, Lukasz;Zhou, Yaoqi
通讯作者：
Zhou, Yaoqi
影响因子：
14.9
作者：
Cheng, J;Randall, AZ;Sweredoski, MJ;Baldi, P
通讯作者：
Baldi, P
影响因子：
64.5
作者：
Mahrus S;Trinidad JC;Barkan DT;Sali A;Burlingame AL;Wells JA
通讯作者：
Wells JA
DOI：
10.1142/s021972000500117x
发表时间：
2005-06-01
影响因子：
1
作者：
Boyd, Sarah E.;Pike, Robert N.;De La Banda, Maria Garcia
通讯作者：
De La Banda, Maria Garcia
影响因子：
14.9
作者：
通讯作者：
--