SLiMPrints: conservation-based discovery of functional motif fingerprints in intrinsically disordered protein regions.
SLiMPrints: conservation-based discovery of functional motif fingerprints in intrinsically disordered protein regions.
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DOI：
10.1093/nar/gks854
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发表时间：
2012-11
影响因子：
14.9
通讯作者：
Edwards RJ
中科院分区：
文献类型：
--
作者：
Davey NE;Cowan JL;Shields DC;Gibson TJ;Coldwell MJ;Edwards RJ
高等真核生物蛋白质组的大部分本质上是无序的，大量的证据表明，这些蛋白质的非结构化区域富含调控相互作用界面。无序相互作用界面的一个主要类别是被称为短线性基序（SLiM）的紧凑和简并模块。由于与SLiM的实验识别和验证相关的困难，我们对这些模块的理解是有限的，主张使用计算方法来集中实验发现。本文评估了使用进化保守作为一种歧视性的技术主题发现。引入统计框架来评估相对保守的残基的意义，量化残基在周围残基保守的情况下具有特定保守水平的可能性。该框架被扩展到评估保守残基分组的意义，这是一个形成SLiMPrints（短线性基序指纹）的基础的度量，一种从头基序发现工具。SLiMPrints识别相对过度约束的近端分组的残基内的固有无序的区域，指示pupillary功能基序。最后，人类蛋白质组进行分析，以创建一组高度保守的推定基序的情况下，包括翻译起始因子eIF2A的一个新的网站，可以通过结合eIF4E调节翻译。
Large portions of higher eukaryotic proteomes are intrinsically disordered, and abundant evidence suggests that these unstructured regions of proteins are rich in regulatory interaction interfaces. A major class of disordered interaction interfaces are the compact and degenerate modules known as short linear motifs (SLiMs). As a result of the difficulties associated with the experimental identification and validation of SLiMs, our understanding of these modules is limited, advocating the use of computational methods to focus experimental discovery. This article evaluates the use of evolutionary conservation as a discriminatory technique for motif discovery. A statistical framework is introduced to assess the significance of relatively conserved residues, quantifying the likelihood a residue will have a particular level of conservation given the conservation of the surrounding residues. The framework is expanded to assess the significance of groupings of conserved residues, a metric that forms the basis of SLiMPrints (short linear motif fingerprints), a de novo motif discovery tool. SLiMPrints identifies relatively overconstrained proximal groupings of residues within intrinsically disordered regions, indicative of putatively functional motifs. Finally, the human proteome is analysed to create a set of highly conserved putative motif instances, including a novel site on translation initiation factor eIF2A that may regulate translation through binding of eIF4E.
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影响因子：
14.9
作者：
Davey NE;Edwards RJ;Shields DC
通讯作者：
Shields DC
影响因子：
30.8
作者：
Cordeddu, Viviana;Di Schiavi, Elia;Pennacchio, Len A.;Ma'ayan, Avi;Sarkozy, Anna;Fodale, Valentina;Cecchetti, Serena;Cardinale, Alessio;Martin, Joel;Schackwitz, Wendy;Lipzen, Anna;Zampino, Giuseppe;Mazzanti, Laura;Digilio, Maria C.;Martinelli, Simone;Flex, Elisabetta;Lepri, Francesca;Bartholdi, Deborah;Kutsche, Kerstin;Ferrero, Giovanni B.;Anichini, Cecilia;Selicorni, Angelo;Rossi, Cesare;Tenconi, Romano;Zenker, Martin;Merlo, Daniela;Dallapiccola, Bruno;Iyengar, Ravi;Bazzicalupo, Paolo;Gelb, Bruce D.;Tartaglia, Marco
通讯作者：
Tartaglia, Marco
影响因子：
56.9
作者：
Dell'Angelica, EC;Klumperman, J;Bonifacino, JS
通讯作者：
Bonifacino, JS
Slimfinder：一种概率方法，用于识别蛋白质中占代表性过多的短线线性基序。
影响因子：
3.7
作者：
Edwards, Richard J.;Davey, Norman E.;Shields, Denis C.
通讯作者：
Shields, Denis C.
影响因子：
14.9
作者：
Finn RD;Mistry J;Tate J;Coggill P;Heger A;Pollington JE;Gavin OL;Gunasekaran P;Ceric G;Forslund K;Holm L;Sonnhammer EL;Eddy SR;Bateman A
通讯作者：
Bateman A