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RG4: Protein Structure and Function in Biomedicine

RG4 aims at understanding the mechanisms of action of proteins based on the study of their biological function and structure in the context of human disease, particularly cardiovascular and neurodegenerative diseases and cancer. This fundamental knowledge is of utmost importance for the three Thematic Lines, since any novel therapy is nowadays supported by a deep scrutiny of the supporting biomolecules and the drug discovery pipeline starts at the protein level. RG4's expertise comprises molecular biology, protein production and purification in various hosts and scales (2-300 Liters); characterization of protein constructs by limited proteolysis and buffer formulation by thermal shift assay; biochemical and biophysical characterization by isothermal titration calorimetry, surface plasmon resonance and spectroscopy; protein structural analysis by X-ray crystallography, SAXS and Cryo-EM; drug discovery and development through screening and identification of drug-like molecules and lead compounds that may become good drug candidates for the pharmaceutical industry.

Main research interests:

  1. Role of the viral latency protein LANA in modulating cellular epigenetic factors to survive and propagate in host cells and its downstream impact on viral oncogenesis;
  2. AAA+ ATPases as anti-cancer drug targets, particularly the RuvBLs' role as components or interactors with multi-protein complexes with diverse cellular functions;
  3. Human enzymes involved in hydrogen sulfide and persulfides metabolism and signaling, related to (colorectal) cancer, cardiovascular disease, and drug-induced kidney toxicity.

Successful collaborations have already been established and more will be promoted within iNOVA4Health with CEDOC and IPOLFG RGs; a strong partnership with in-house satellite labs from Merck KGaA and Bayer, involved in structure-based drug design and development of antibody-based therapies.

 

Keywords: Structural and Functional Biology; Cancer Biology and therapy; Drug discovery and development; Protein Biophysics

Latest Publications

Gizardin-Fredon H, Santo PE, Chagot ME, Charpentier B, Bandeiras TM, Manival X, Hernandez-Alba O, Cianférani S. (2024). Denaturing mass photometry for rapid optimization of chemical protein-protein cross-linking reactions. Nat Commun. Apr 25;15(1):3516

Dos Santos Morais R, Santo PE, Ley M, Schelcher C, Abel Y, Plassart L, Deslignière E, Chagot ME, Quinternet M, Paiva ACF, Hessmann S, Morellet N, M F Sousa P, Vandermoere F, Bertrand E, Charpentier B, Bandeiras TM, Plisson-Chastang C, Verheggen C, Cianférani S, Manival X. (2022) Deciphering cellular and molecular determinants of human DPCD protein in complex with RUVBL1/RUVBL2 AAA-ATPases. J Mol Biol. Oct 15;434(19):167760

Abel Y, Paiva ACF, Bizarro J, Chagot ME, Santo PE, Robert MC, Quinternet M, Vandermoere F, Sousa PMF, Fort P, Charpentier B, Manival X, Bandeiras TM, Bertrand E, Verheggen C. (2021) NOPCHAP1 is a PAQosome cofactor that helps loading NOP58 on RUVBL1/2 during box C/D snoRNP biogenesis. Nucleic Acids Res. Jan 25;49(2):1094-1113

Zuhra K, Sousa PMF, Paulini G, Lemos AR, Kalme Z, Bisenieks I, Bisenieks E, Vigante B, Duburs G, Bandeiras TM, Saso L, Giuffrè A, Vicente JB (2019) Screening Pyridine Derivatives against Human Hydrogen Sulfide-synthesizing Enzymes by Orthogonal Methods. Scientific Reports 9(1):684

Costa J, Streich L, Pinto S, Pronto-Laborinho A, Nimtz M, Conradt HS, Carvalho M (2019) Exploring Cerebrospinal Fluid IgG N-Glycosylation as Potential Biomarker for Amyotrophic Lateral Sclerosis. Molecular Neurobiology 56(8):5729-5739

Fonseca BM, Silva L, Trindade IB, Moe E, Matias PM, Louro RO, Paquete CM (2019) Optimizing Electroactive Organisms: The Effect of Orthologous Proteins. Frontiers in Energy Research (in press)

Maurizy C, Quinternet M, Abel Y, Verheggen C, Santo PE, Bourguet M, C F Paiva A, Bragantini B, Chagot ME, Robert MC, Abeza C, Fabre P, Fort P, Vandermoere F, MF Sousa P, Rain JC, Charpentier B, Cianférani S, Bandeiras TM, Pradet-Balade B, Manival X, Bertrand E (2018) The RPAP3-Cterminal domain identifies R2TP-like quaternary chaperones. Nature Communications 9(1):2093

Trindade IB, Silva JM, Fonseca BM, Catarino T, Fujita M, Matias PM, Moe E, Louro RO (2018) Structure and reactivity of a siderophore-interacting protein from the marine bacterium Shewanella reveals unanticipated functional versatility. The Journal of Biological Chemistry 294:157-167