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General research interest

Peter Tompa contributed significantly to the recognition and description of structural disorder in proteins from the very beginning of this research field. Studying and explaining this structural phenomenon remains the main focus of his research, with the aim to understand better the structure-function relations of proteins. Intrinsic protein disorder represents a new functionality that is fundamentally different from the traditional structure-function paradigm. Understanding how intrinsically disordered proteins (IDPs) function requires new conceptual approaches where the aim is not only to determine one structure, but rather describing how function arises from the multitude of different structural states. In order to extend the structure-function paradigm, we use the combination of bioinformatics, theoretical, in vitro and in vivo techniques and interpret the results comprehensively. Our studies include general, genome-level investigations as well as detailed structure-function analysis of selected proteins.

Major research projects

The connection of protein disorder and chaperone function was described in our laboratory through the detailed analysis of the disordered plant chaperone ERD14. Using in cell NMR measurements we can characterize the structural ensemble of ERD14 under physiological conditions while in parallel measurements we examine the stress-resistance of E. coli cells overexpressing ERD14. We aim to uncover the details of the structure-function relations of the chaperone function of this protein.

We also investigate the apparent contradiction between the proteolytic sensitivity of IDPs and their in vivo functionality. Using the in vivo system we developed for the study of the chaperone function of ERD14, we can test the in vivo half-life of this protein. Since we already verified that ERD14 is disordered in the cells, by following the levels of the protein after stopping the translation we can determine the lifetime of a disordered protein in vivo. Our first results show that due to the strict regulation of the proteolytic systems, the disordered proteins are protected from uncontrolled degradation.

The connection between intrinsic disorder and the chaperone function is further investigated through the study of a Nudix hydrolase of Deinococcus radiodurans. Important enzymes that contain disordered regions functioning as intramolecular chaperones may play a crucial role in the extreme stress tolerance of this bacterium. Our results confirm the intramolecular chaperone effect of such a disordered region, but also indicate its capability of RNA binding. The physiological importance of this feature is the subject of our ongoing research.

Our bioinformatics studies mostly concentrate on the short recognition motifs found in different IDPs. Most of IDPs function through molecular recognition mediated by short sequence/structural motifs (Eukaryotic Linear Motifs, ELM, Molecular Recognition Features, MoRFs). We perform detailed analysis of these sequences and try to identify the main features that differentiate recognition motifs from amyloidogenic and immunoreactive elements. The importance of the question is underlined by the observation that these short motifs are sequentially similar, but are under different evolutionary pressure.

Collaborations

Kju Hon Han, KRIBB, Dél-Korea

Robert Konrat, Institute of Biomolecular Structural Chemistry, University of Vienna

Richard G. Pestell, Thomas Jefferson University, USA; Sidney Kimmel Cancer Center, USA

Laszlo Poppe, Budapest University of Technology and Economics

Lab equipment

Akta Explorer FPLC system

Fluorescence plate reader (Synergy)

Spectrophotometer (Jasco)

Fluorometer (Jasco)

Gradient PCR (Eppendorf)

TransBlot turbo (BioRad)

SnapID (Millipore)

Education

PhD course on intrinsically disordered proteins (ELTE)

MSc and BSc students from ELTE, PPKE, BME

Group leader

Dr. Tompa Péter, scientific advisor, group leader

Members

Tantos Ágnes                          Senior research fellow

Schád Éva                                 Research fellow

Némethné Szabó Beáta         Research fellow

Horváth Tamás                      PhD student

Mészáros Attila                      PhD student

Murvai Nikoletta                   PhD student