Peter Tompa Lab

Research focus

​In the focus of our research is the phenomenon of structural disorder of proteins. It has been recently recognized that regions of proteins or even full-length proteins exist and function without well-defined 3D structures, which challenged the classical structure-function paradigm and called for studies aiming at understanding this phenomenon in detail. These studies have shown that structural disorder is prevalent in eukaryotic proteomes and disordered proteins carry out unique functions. Due to their frequent involvement in regulatory and signaling functions, structural disorder also plays important roles in serious diseases, such as cancer and neurodegeneration.

The study of structural disorder has already progressed way beyond simply establishing the disordered status of a protein. The current idea is that detailed experimental and theoretical characterization of the structural ensemble of disordered proteins in isolation, their structure in complex with their physiological partner(s), and the thermodynamics and kinetics of their interactions with their partners, hold the key to understanding these proteins and extending the structure –function paradigm to the disordered state. In this spirit, we undertake three different lines of research to push the frontiers of the field of disorder.

Our first project aims to extend the paradigm of disordered chaperones to cellular conditions. We suggested some time ago that fully disordered proteins or disordered regions of classical chaperones can have chaperone function on their own. We underscored this tenet by observations on a plant dehydrin, ERD14. Here we seek to elucidate details of the underlying mechanism by making: i) proteomic studies to determine the physiological partners of this disordered chaperone, ii) in-cell NMR studies to see the structure and interactions of ERD14 in live plant cells, and iii) detailed structure-function studies to see which sequence elements are involved in transient binding to the partner and how the interplay of induced folding and disorder in the bound state contribute to chaperone activity.

We also aim to understand the structure-function relationship of very large (“oversized”) proteins, practically neglected from a structural point of view thus far. Structural biology has traditionally addressed the structure of small folded proteins, whereas the field of structural disorder has focused on either fully disordered proteins/regions or short disordered elements that undergo induced folding in the presence of their partner. Here we would like to probe into the structure of the very large transcriptional co-activator CREB-binding protein (CBP), by addressing its structure by means traditionally applied in the case of protein complexes. CBP has about seven domains and disordered linker regions connecting them, the topology of which will be outlined by a combination of high-resolution (NMR, X-ray) and low-resolution (MS, EM, AFM) techniques.

In the third project we want to demonstrate that our knowledge on the structure and function of IDPs has already progressed to a state where we can describe their function in terms of binding motifs and linker elements. To this end, we will systematically alter, replace and mutate binding motifs and connecting regions of calpastatin, the disordered inhibitor of the enzyme calpain, to explore how much we can diverge from the wild-type sequence without compromising function. Functional effects of such extensive mutations will be approached by in vitro binding and inhibitory assays, by solving the structure of the enzyme-inhibitor complex and also by in vivo assays of the cellular effects of mutations.


SnapShot: Intrinsic Structural DisorderGuha Roy M, Pauwels K, Tompa PCELL, 161, 1230-1230 e1, 2015
From protein sequence to dynamics and disorder with DynaMineCilia E, Pancsa R, Tompa P, Lenaerts T, Vranken WNature Communications, 4, 2741, 2013
Unstructural biology coming of ageTompa PCURRENT OPINION IN STRUCTURAL BIOLOGY, 21, 419-25, 2011
Dual coding in alternative reading frames correlates with intrinsic protein disorderKovacs E, Tompa P, Liliom K, Kalmar LPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 107, 5429-34, 2010


A million peptide motifs for the molecular biologist

17/07/2014 - There might be over a million instances of peptide motifs in the human proteome. While this number suggests that peptide motifs are numerous and the most understudied functional module in the cell, it also holds great opportunities for new discoveries.

Movements of proteins can be predicted from their amino acid sequence

25/11/2013 - Researchers of the VIB department of Structural Biology and the ‘Interuniversity Institute of Bioinformatics in Brussels (IB2)’, have developed a method to predict how much the backbone chain of a protein moves based on only its amino acid sequence.

The unstructural biologist

01/06/2011 - Interview with Peter Tompa, successor of Lode Wyns as Director of the VIB Department of Structural Biology Brussels, Vrije Universiteit Brussel.

Ingrid Lieten, Flemish Minister of Innovation, recruits top scientist Peter Tompa to VIB and Vrije Universiteit Brussel

13/05/2011 - On Wednesday, 11 May 2011, minister Ingrid Lieten, has presented Peter Tompa as the successor of Lode Wyns as Director of the VIB Department of Structural Biology at the Vrije Universiteit Brussel.

Peter Tompa

Peter Tompa

Research area(s)


​​PhD: ELTE University, Budapest, Hungary, 1991
D.Sc. Hungarian Academy of Sciences, Budapest, Hungary, 2006
Postdoc in ECUST Univ. China - Weizmann Inst. Israel - St. Jude Children's Hosp., US - Tokyo Univ., Japan
Pi, Inst. Enzymology, Budapest, Hungary - 2006-2011
Deputy Director Inst. Enzymology, Hungary - 2007-2009
VIB director from May 2011 till December 2015
VIB group leader since May, 2011

Contact Info

VIB Structural Biology Research CenterVUBBuilding EPleinlaan 2 1050 BRUSSELRoute description