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Structural Disorder and Molecular Recognition

Head Sonia LONGHI

The group focuses on the identification, characterization and elucidation of the functional role of disordered regions within proteins relevant in terms of human health. In particular, we are interested in proteins of the replicative complex of human pathogenic viruses, such as the measles virus and the recently emerged Nipah and Hendra viruses.

During the last fifteen years, the so-called structure-function paradigm was challenged by the discovery of intrinsically disordered proteins (IDPs), i.e. proteins that lack stable secondary and tertiary structure under physiological conditions of pH and salinity in the absence of a partner or ligand. Nevertheless, they are functional and are extremely abundant in living world. The group played a pioneering role in discovering that the nucleoprotein (N) and phosphoprotein (P) of measles virus posses long disordered regions (up to 250 residues), and subsequently extended these results to the N and P proteins from the Nipah and Hendra viruses, two recently emerged BSL4 pathogens. This discovery opens numerous interesting perspectives from a fundamental point of view but also in terms of potential therapeutic applications. The originality and main strength of the researches carried out by the group resides in the multidisciplinarity through the integration of bioinformatics, biochemistry, biophysics and structural biology.

The research activities of the team embrace four major axes:

  • The identification of disordered regions and the elucidation of the functional role of structural disorder within the replicative machinery of paramyxoviruses and its relevance in virus-host cell interactions.
  • The unraveling of the molecular mechanisms of folding coupled to binding events.
  • The understanding of the molecular bases of specificity and affinity in partner recognition by intrinsically disordered proteins (IDPs).
  • The discovery of compounds capable of blocking crucial interactions involving intrinsically disordered regions (IDRs).

Antoine Schramm
Christophe BIGNON
Francesca TROILO

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