- Modulation of re-initiation of measles virus transcription at intergenic regions by PXD to NTAIL binding strength. (2016) Bloyet LM, Brunel J, Dosnon M, Hamon V, Erales J, Gruet A, Lazert C, Bignon C, Roche P, Longhi S and Gerlier D. PLoS Pathog 12 e1006058 PMID:27936158
- DisProt 7.0: a major update of the database of disordered proteins (2016) Piovesan D, Tabaro F, Micetic I, Necci M, Quaglia F, Oldfield C, Aspromonte MC, Norman Davey NE, Davidovic R, Dosztanyi Z, Elofsson A, Gasparini A, Hatos A, Kajava AV, Kalmar L, Leonardi E, Lazar T, Macedo-Ribeiro S, Macossay Castillo M, Meszaros A, Minervini G, Murvai N, Pujols J, Roche DB, Salladini E, Schad E, Schramm A, Szabo B, Tantos A, Tonello F, Tsirigos KD, Veljkovic N, Ventura S, Vranken W, Warholm P, Uversky VN, Dunker AK, Longhi S, Tompa P and Tosatto SCE.. Nucleic Acid Research 45(D1) D219-D227 PMID:27899601
- How disordered is my protein and what is its disorder for? A guide through the dark side of the protein universe. (2016) Lieutaud P, Ferron F, Uversky AV, Kurgan L, Uversky VN and Longhi S.. Intrinsically Disordered Proteins 4:1 e1259708 PMID:0
- Predicting Conformational Disorder. (2016) Lieutaud P, Ferron F, Longhi S. Methods Mol Biol 1415 265-99 PMID:27115638
- Identification and Structural Characterization of an Intermediate in the Folding of the Measles Virus X domain. (2016) Bonetti D, Camilloni C, Visconti L, Longhi S, Brunori M, Vendruscolo M, Gianni S. J Biol Chem 291 10886-92 PMID:27002146
- Fuzzy regions in an intrinsically disordered protein impair protein-protein interactions. (2016) Gruet A, Dosnon M, Blocquel D, Brunel J, Gerlier D, Das RK, Bonetti D, Gianni S, Fuxreiter M, Longhi S, Bignon C. FEBS J 283 576-94 PMID:26684000
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).