Understanding eukaryotic linear motifs and their role in cell signaling and regulation.
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.
Diella
Francesca
F
Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Haslam
Niall
N
Chica
Claudia
C
Budd
Aidan
A
Michael
Sushama
S
Brown
Nigel P
NP
Trave
Gilles
G
Gibson
Toby J
TJ
D000818:Animals; D002468:Cell Physiological Phenomena; D004721:Endoplasmic Reticulum / Q000502:physiology; D006706:Homeostasis; D008322:Mammals; D008954:Models, Biological; D011506:Proteins / Q000502:physiology; D015203:Reproducibility of Results; D015398:Signal Transduction
D011506:Proteins