A single buried cysteine acts as a hydrophobic stabilizer of a folding intermediate and transition state in the MATH domain of SPOP @article{ 11573_1738574, author = {Pagano, Livia and Diop, Awa and Pennacchietti, Valeria and Di Felice, Mariana and Ventura, Eduarda S. and Toso, Julian and Toto, Angelo and Gianni, Stefano}, title = {A single buried cysteine acts as a hydrophobic stabilizer of a folding intermediate and transition state in the MATH domain of SPOP}, year = {2025}, journal = {PROTEIN SCIENCE}, volume = {34}, abstract = {Cysteine is a highly conserved amino acid with diverse roles in protein function. Whilst its role in the formation of disulfide bridges is well characterized, the contribution of isolated cysteines in protein folding is by and large unexplored. Here we investigate the impact of cysteine residues on the folding pathway of the MATH domain in the SPOP protein by comparing wild-type and serine mutants. Through kinetic analyses, we demonstrate that a buried cysteine residue stabilizes both an early folding intermediate and the main transition state. Most notably, such effects are disrupted upon substitution with serine but preserved with alanine. These findings suggest that, in certain structural contexts, cysteine behaves as a hydrophobic rather than a polar residue. Our results challenge the traditional classification of cysteine as a polar amino acid and highlight its unique contributions to protein folding, with implications for protein engineering and structural biology.}, keywords = {MATH domain; cysteine; kinetics; protein folding; site‐directed mutagenesis}, doi = {10.1002/pro.70138}, number = {6} } .

Paola Pietrangeli, Lucia Marcocci, Valeria Pennacchietti, Awa Diop, Mariana Di Felice, Livia Pagano, Francesca Malagrinò, Angelo Toto, Maurizio Brunori, Stefano Gianni (2024). The Mechanism of Folding of Human Frataxin in Comparison to the Yeast Homologue – Broad Energy Barriers and the General Properties of the Transition State . Journal of Molecular Biology.

Mariana Di Felice, Livia Pagano, Valeria Pennacchietti, Awa Diop, Paola Pietrangeli, Lucia Marcocci, Sara Di Matteo, Francesca Malagrinò, Angelo Toto, Stefano Gianni (2024). The binding selectivity of the C-terminal SH3 domain of Grb2, but not its folding pathway, is dictated by its contiguous SH2 domain . Journal of Biological Chemistry.

The binding selectivity of the C-terminal SH3 domain of Grb2, but not its folding pathway, is dictated by its contiguous SH2 domain @article{ 11573_1706810, author = {Di Felice, Mariana and Pagano, Livia and Pennacchietti, Valeria and Diop, Awa and Pietrangeli, Paola and Marcocci, Lucia and Di Matteo, Sara and Malagrinò, Francesca and Toto, Angelo and Gianni, Stefano}, title = {The binding selectivity of the C-terminal SH3 domain of Grb2, but not its folding pathway, is dictated by its contiguous SH2 domain}, year = {2024}, journal = {THE JOURNAL OF BIOLOGICAL CHEMISTRY}, volume = {300}, keywords = {double-mutant cycle; kinetics; multidomain protein; mutagenesis; protein‐protein interaction}, doi = {10.1016/j.jbc.2024.107129}, number = {4} } .

The mechanism of folding of human frataxin in comparison to the yeast homologue – broad energy barriers and the general properties of the transition state @article{ 11573_1707732.6, author = {Pietrangeli, Paola and Marcocci, Lucia and Pennacchietti, Valeria and Diop, Awa and Di Felice, Mariana and Pagano, Livia and Malagrinò, Francesca and Toto, Angelo and Brunori, Maurizio and Gianni, Stefano}, title = {The mechanism of folding of human frataxin in comparison to the yeast homologue – broad energy barriers and the general properties of the transition state}, year = {2024}, journal = {JOURNAL OF MOLECULAR BIOLOGY}, volume = {436}, keywords = {energy landscape; kinetics; linear-free energy relationships; mutagenesis; protein folding}, doi = {10.1016/j.jmb.2024.168555}, number = {10} }.

Awa Diop, Paola Pietrangeli, Valeria Pennacchietti, Livia Pagano, Angelo Toto, Mariana Di Felice, Sara Di Matteo, Lucia Marcocci, Francesca Malagrinò, Stefano Gianni (2023). Addressing the Binding Mechanism of the Meprin and TRAF-C Homology Domain of the Speckle-Type POZ Protein Using Protein Engineering . International Journal of Molecular Sciences.

Awa Diop, Paola Pietrangeli, Valeria Pennacchietti, Livia Pagano, Angelo Toto, Mariana Di Felice, Sara Di Matteo, Lucia Marcocci, Francesca Malagrinò, Stefano Gianni (2023). Addressing the Binding Mechanism of the Meprin and TRAF-C Homology Domain of the Speckle-Type POZ Protein Using Protein Engineering . International Journal of Molecular Sciences.

Awa Diop, Paola Pietrangeli, Caterina Nardella, Valeria Pennacchietti, Livia Pagano, Angelo Toto, Mariana Di Felice, Sara Di Matteo, Lucia Marcocci, Francesca Malagrinò, et al. (2023). Biophysical Characterization of the Binding Mechanism between the MATH Domain of SPOP and Its Physiological Partners . International Journal of Molecular Sciences.

Awa Diop, Paola Pietrangeli, Caterina Nardella, Valeria Pennacchietti, Livia Pagano, Angelo Toto, Mariana Di Felice, Sara Di Matteo, Lucia Marcocci, Francesca Malagrinò, et al. (2023). Biophysical Characterization of the Binding Mechanism between the MATH Domain of SPOP and Its Physiological Partners . International Journal of Molecular Sciences.

Daniele Santorelli, Lucia Marcocci, Valeria Pennacchietti, Caterina Nardella, Awa Diop, Paola Pietrangeli, Livia Pagano, Angelo Toto, Francesca Malagrinò, Stefano Gianni (2023). Understanding the molecular basis of folding cooperativity through a comparative analysis of a multidomain protein and its isolated domains . Journal of Biological Chemistry.

Biophysical characterization of the binding mechanism between the MATH domain of SPOP and its physiological partners @article{ 11573_1683686, author = {Diop, Awa and Pietrangeli, Paola and Nardella, Caterina and Pennacchietti, Valeria and Pagano, Livia and Toto, Angelo and Di Felice, Mariana and Di Matteo, Sara and Marcocci, Lucia and Malagrinò, Francesca and Gianni, Stefano}, title = {Biophysical characterization of the binding mechanism between the MATH domain of SPOP and its physiological partners}, year = {2023}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {24}, keywords = {kinetics; protein–protein interactions; MATH domain; speckle-type POZ protein}, doi = {10.3390/ijms241210138}, number = {12} } .

Nardella, Caterina and Pagano, Livia and Pennacchietti, Valeria and Felice, Mariana Di and Matteo, Sara Di and Diop, Awa and Malagrinò, Francesca and Marcocci, Lucia and Pietrangeli, Paola and Gianni, Stefano and Toto, Angelo(2023). An intramolecular energetic network regulates ligand recognition in a SH2 domain . PROTEIN SCIENCE. 32. (8).

Pennacchietti, Valeria and Pagano, Livia and Malagrinò, Francesca and Diop, Awa and Di Felice, Mariana and Di Matteo, Sara and Marcocci, Lucia and Pietrangeli, Paola and Toto, Angelo and Gianni, Stefano(2023). Characterization of the folding and binding properties of the PTB domain of FRS2 with phosphorylated and unphosphorylated ligands . ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS. 745.

Addressing the binding mechanism of the Meprin and TRAF-C hmology domain of the Speckle-Type POZ protein using protein engineering @article{ 11573_1695759, author = {Diop, Awa and Pietrangeli, Paola and Pennacchietti, Valeria and Pagano, Livia and Toto, Angelo and Di Felice, Mariana and Di Matteo, Sara and Marcocci, Lucia and Malagrinò, Francesca and Gianni, Stefano}, title = {Addressing the binding mechanism of the Meprin and TRAF-C hmology domain of the Speckle-Type POZ protein using protein engineering}, year = {2023}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {24}, keywords = {kinetics; protein–protein interactions; MATH domain; speckle-type POZ protein; site-directed mutagenesis}, doi = {10.3390/ijms242417364}, number = {24} } .

Santorelli, Daniele and Marcocci, Lucia and Pennacchietti, Valeria and Nardella, Caterina and Diop, Awa and Pietrangeli, Paola and Pagano, Livia and Toto, Angelo and Malagrino, Francesca and Gianni, Stefano(2023). Understanding the molecular basis of folding cooperativity through a comparative analysis of a multidomain protein and its isolated domains . THE JOURNAL OF BIOLOGICAL CHEMISTRY. 299. (3). p. 1--8. American Society for Biochemistry and Molecular Biology Inc.

Awa Diop, Daniele Santorelli, Francesca Malagrinò, Caterina Nardella, Valeria Pennacchietti, Livia Pagano, Lucia Marcocci, Paola Pietrangeli, Stefano Gianni, Angelo Toto (2022). SH2 Domains: Folding, Binding and Therapeutical Approaches . International Journal of Molecular Sciences.

Awa Diop, Daniele Santorelli, Francesca Malagrinò, Caterina Nardella, Valeria Pennacchietti, Livia Pagano, Lucia Marcocci, Paola Pietrangeli, Stefano Gianni, Angelo Toto (2022). SH2 Domains: Folding, Binding and Therapeutical Approaches . International Journal of Molecular Sciences.

Caterina Nardella, Angelo Toto, Daniele Santorelli, Livia Pagano, Awa Diop, Valeria Pennacchietti, Paola Pietrangeli, Lucia Marcocci, Francesca Malagrinò, Stefano Gianni (2022). Folding and Binding Mechanisms of the SH2 Domain from Crkl . Biomolecules.

Caterina Nardella, Angelo Toto, Daniele Santorelli, Livia Pagano, Awa Diop, Valeria Pennacchietti, Paola Pietrangeli, Lucia Marcocci, Francesca Malagrinò, Stefano Gianni (2022). Folding and Binding Mechanisms of the SH2 Domain from Crkl . Biomolecules.

Francesca Malagrinò, Awa Diop, Livia Pagano, Caterina Nardella, Angelo Toto, Stefano Gianni(2022). Unveiling induced folding of intrinsically disordered proteins – Protein engineering, frustration and emerging themes . Current Opinion in Structural Biology. 72. p. 153--160. Elsevier {BV}

Francesca Malagrinò, Valeria Pennacchietti, Daniele Santorelli, Livia Pagano, Caterina Nardella, Awa Diop, Angelo Toto, Stefano Gianni (2022). On the Effects of Disordered Tails, Supertertiary Structure and Quinary Interactions on the Folding and Function of Protein Domains . Biomolecules.

Pagano, Livia and Pennacchietti, Valeria and Diop, Awa and Santorelli, Daniele and Pietrangeli, Paola and Marcocci, Lucia and Nardella, Caterina and Malagrinò, Francesca and Toto, Angelo and Gianni, Stefano(2022). Exploring the effect of tethered domains on the folding of Grb2 protein . ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS.

Toto, Angelo and Malagrinò, Francesca and Nardella, Caterina and Pennacchietti, Valeria and Pagano, Livia and Santorelli, Daniele and Diop, Awa and Gianni, Stefano(2022). Characterization of early and late transition states of the folding pathway of a SH2 domain . PROTEIN SCIENCE. 31. (6).

On the effects of disordered tails, supertertiary structure and quinary interactions on the folding and function of protein domains @article{ 11573_1607647, author = {Malagrino, F. and Pennacchietti, V. and Santorelli, D. and Pagano, L. and Nardella, C. and Diop, A. and Toto, A. and Gianni, S.}, title = {On the effects of disordered tails, supertertiary structure and quinary interactions on the folding and function of protein domains}, year = {2022}, publisher = {MDPI}, journal = {BIOMOLECULES}, volume = {12}, keywords = {Crowding; IDPs; multidomain proteins; protein–protein interactions}, doi = {10.3390/biom12020209} } .

Folding and binding mechanisms of the SH2 domain from Crkl @article{ 11573_1651291, author = {Nardella, Caterina and Toto, Angelo and Santorelli, Daniele and Pagano, Livia and Diop, Awa and Pennacchietti, Valeria and Pietrangeli, Paola and Marcocci, Lucia and Malagrinò, Francesca and Gianni, Stefano}, title = {Folding and binding mechanisms of the SH2 domain from Crkl}, year = {2022}, journal = {BIOMOLECULES}, volume = {12}, keywords = {kinetics; fluorescence; site-directed mutagenesis; protein–protein interactions; SH2 domains; Crkl; Paxillin}, doi = {10.3390/biom12081014}, number = {8} } .

Diop, Awa and Santorelli, Daniele and Malagrinò, Francesca and Nardella, Caterina and Pennacchietti, Valeria and Pagano, Livia and Marcocci, Lucia and Pietrangeli, Paola and Gianni, Stefano and Toto, Angelo(2022). SH2 Domains: folding, binding and therapeutical approaches . INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 23. (24).

Francesca Malagrinò, Valeria Pennacchietti, Daniele Santorelli, Livia Pagano, Caterina Nardella, Awa Diop, Angelo Toto, Stefano Gianni (2022). On the Effects of Disordered Tails, Supertertiary Structure and Quinary Interactions on the Folding and Function of Protein Domains . Biomolecules.

Malagrinò, F., Pennacchietti, V., Santorelli, D., Pagano, L., Nardella, C., Diop, A., Toto, A., Gianni, S.(2022). On the Effects of Disordered Tails, Supertertiary Structure and Quinary Interactions on the Folding and Function of Protein Domains . Biomolecules. 12. (2).

Malagrinò, F., Diop, A., Pagano, L., Nardella, C., Toto, A., Gianni, S.(2022). Unveiling induced folding of intrinsically disordered proteins – Protein engineering, frustration and emerging themes . Current Opinion in Structural Biology. 72. p. 153-160.

Nicolas Papageorgiou, Afroditi Vaitsopoulou, Awa Diop, Thi Hong Van Nguyen, Bruno Canard, Karine Alvarez, François Ferron(2021). Observation of arenavirus nucleoprotein heptamer assembly . FEBS Open Bio. 11. (4). p. 1076--1083. Wiley

Papageorgiou, N. and Vaitsopoulou, A. and Diop, A. and Nguyen, T. H. V. and Canard, B. and Alvarez, K. and Ferron, F.(2021). Observation of arenavirus nucleoprotein heptamer assembly . FEBS OPENBIO. 11. (4). p. 1076--1083. John Wiley and Sons Inc

Malagrinò, Francesca and Diop, Awa and Pagano, Livia and Nardella, Caterina and Toto, Angelo and Gianni, Stefano(2021). Unveiling induced folding of intrinsically disordered proteins - Protein engineering, frustration and emerging themes . CURRENT OPINION IN STRUCTURAL BIOLOGY. 72. p. 160--160.

Papageorgiou, N., Vaitsopoulou, A., Diop, A., Nguyen, T.H.V., Canard, B., Alvarez, K., Ferron, F.(2021). Observation of arenavirus nucleoprotein heptamer assembly . FEBS Open Bio. 11. (4). p. 1076-1083.

Yazen Yaseen and Awa Diop and Fr{\'{e}}d{\'{e}}rique Gancel and Max B{\'{e}}chet and Philippe Jacques and Djamel Drider(2018). Polynucleotide phosphorylase is involved in the control of lipopeptide fengycin production in Bacillus subtilis . Archives of Microbiology. 200. (5). p. 783--791. Springer Science and Business Media {LLC}

Yaseen, Y., Diop, A., Gancel, F., Béchet, M., Jacques, P., Drider, D.(2018). Polynucleotide phosphorylase is involved in the control of lipopeptide fengycin production in Bacillus subtilis . Archives of Microbiology. 200. (5). p. 783-791.

Diop, Awa(2024). Unravelling the mechanistic details of a protein recognition domain interactions with short linear motifs: binding and inhibition mechanisms . Università degli Studi di Roma "La Sapienza

Yaseen, Y. and Diop, A. and Gancel, F. and Bechet, M. and Jacques, P. and Drider, D.(2018). Polynucleotide phosphorylase is involved in the control of lipopeptide fengycin production in Bacillus subtilis . 5783--791Springer Verlag