Functional dissection of an intrinsically disordered protein: Understanding the roles of different domains of Knr4 protein in protein-protein interactions
2010
Timmers Dagkessamanskaya, Adilya | Durand, Fabien | Uversky, Vladimir N. | Binda, Matteo | Lopez, Frédéric | El Azzouzi, Karim | François, Jean Marie | Martin-Yken, Hélène | Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP) ; Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse) ; Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS) | Université de Toulouse (UT) | Institute for Biological Instrumentation ; Russian Academy of Sciences [Moscow] (RAS) | Indiana University System | Université de Fribourg = University of Fribourg (UNIFR) | Centre Hospitalier Universitaire de Toulouse (CHU Toulouse) | French Ministry of Research ACI-BCMS 2004-2005 ; National Institute of Health R01 LM007688-01A1 R01 GM071714-01A2 ; National Science Foundation EF 0849803 ;Russian Academy of Sciences ; IUPUI Signature Centers Initiative
International audience
显示更多 [+] 显示较少 [-]英语. Knr4, recently characterized as an intrinsically disordered Saccharomyces cerevisiae protein, participates in cell wall formation and cell cycle regulation. It is constituted of a functional central globular core flanked by a poorly structured N-terminal and large natively unfolded C-terminal domains. Up to now, about 30 different proteins have been reported to physically interact with Knr4. Here, we used an in vivo two-hybrid system approach and an in vitro surface plasmon resonance (BIAcore) technique to compare the interaction level of different Knr4 deletion variants with given protein partners. We demonstrate the indispensability of the N-terminal domain of Knr4 for the interactions. On the other hand, presence of the unstructured C-terminal domain has a negative effect on the interaction strength. In protein interactions networks, the most highly connected proteins or "hubs" are significantly enriched in unstructured regions, and among them the transient hub proteins contain the largest and most highly flexible regions. The results presented here of our analysis of Knr4 protein suggest that these large disordered regions are not always involved in promoting the protein-protein interactions of hub proteins, but in some cases, might rather inhibit them. We propose that this type of regions could prevent unspecific protein interactions, or ensure the correct timing of occurrence of transient interactions, which may be of crucial importance for different signaling and regulation processes.
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