Flexible nets: disorder and induced fit in the associations of p53 and 14-3-3 with their partners.
BACKGROUND
Proteins are involved in many interactions with other proteins leading to networks that regulate and control a wide variety of physiological processes. Some of these proteins, called hub proteins or hubs, bind to many different protein partners. Protein intrinsic disorder, via diversity arising from structural plasticity or flexibility, provide a means for hubs to associate with many partners (Dunker AK, Cortese MS, Romero P, Iakoucheva LM, Uversky VN: Flexible Nets: The roles of intrinsic disorder in protein interaction networks. FEBS J 2005, 272:5129-5148).


RESULTS
Here we present a detailed examination of two divergent examples: 1) p53, which uses different disordered regions to bind to different partners and which also has several individual disordered regions that each bind to multiple partners, and 2) 14-3-3, which is a structured protein that associates with many different intrinsically disordered partners. For both examples, three-dimensional structures of multiple complexes reveal that the flexibility and plasticity of intrinsically disordered protein regions as well as induced-fit changes in the structured regions are both important for binding diversity.


CONCLUSIONS
These data support the conjecture that hub proteins often utilize intrinsic disorder to bind to multiple partners and provide detailed information about induced fit in structured regions.
Oldfield
Christopher J
CJ
Center for Computational Biology and Bioinformatics, Indiana University Schools of Medicine and Informatics, 410 W, 10th Street, Indianapolis, IN 46202, USA. cjoldfie@iupui.edu
Meng
Jingwei
J
Yang
Jack Y
JY
Yang
Mary Qu
MQ
Uversky
Vladimir N
VN
Dunker
A Keith
AK
D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D015398:Signal Transduction / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D048948:14-3-3 Proteins; D016159:Tumor Suppressor Protein p53