Understanding eukaryotic linear motifs and their role in cell signaling and regulation

被引:262
作者
Diella, Francesca [1 ]
Haslam, Niall [1 ]
Chica, Claudia [1 ]
Budd, Aidan [1 ]
Michael, Sushama [1 ]
Brown, Nigel P. [2 ]
Trave, Gilles [3 ]
Gibson, Toby J. [1 ]
机构
[1] European Mol Biol Lab, Struct & Computat Biol Unit, D-69117 Heidelberg, Germany
[2] Heidelberg Univ, BIOQUANT, D-69120 Heidelberg, Germany
[3] ESBS, F-67412 Illkirch Graffenstaden, France
来源
FRONTIERS IN BIOSCIENCE-LANDMARK | 2008年 / 13卷
关键词
linear motif; globular domain; cell regulation; cell signaling; protein interaction; phosphopeptide; natively disordered protein; prediction methods; network topology; protein complex; review;
D O I
10.2741/3175
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
It is now clear that a detailed picture of cell regulation requires a comprehensive understanding of the abundant short protein motifs through which signaling is channeled. The current body of knowledge has slowly accumulated through piecemeal experimental investigation of individual motifs in signaling. Computational methods contributed little to this process. A new generation of bioinformatics tools will aid the future investigation of motifs in regulatory proteins, and the disordered polypeptide regions in which they frequently reside. Allied to high throughput methods such as phosphoproteomics, signaling networks are becoming amenable to experimental deconstruction. In this review, we summarise the current state of linear motif biology, which uses low affinity interactions to create cooperative, combinatorial and highly dynamic regulatory protein complexes. The discrete deterministic properties implicit to these assemblies suggest that models for cell regulatory networks in systems biology should neither be overly dependent on stochastic nor on smooth deterministic approximations.
引用
收藏
页码:6580 / 6603
页数:24
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