Structural biology of neurotrophins and proneurotrophins
Structural and functional characterization of neurotrophins, proneurotrophins and their pathological mutants. Structural studies of the role of endogenous biomolecules as modulators of neurotrophins and proneurotrophins.
Studies on the evolution of human proneurotrophins, as intrinsically disordered proteins, by bioinformatics.
Cloning, mutagenesis, recombinant expression of human proneurotrophins in inclusion bodies; refolding and purification by chromatographic systems. Production of mature neurotrophins mediated by tryptic digestion and purification.
Biophysical and structural characterization of the effect on the conformation of human neurotrophins and proneurotrophins of pathological mutations by molecular dynamics, limited proteolysis, DSF, Fluorescence and SAXS. Analysis of their interaction with ligands of physiological and pathological relevance, using SAXS, DSF, fluorescence, GCI and ITC.
– Covaceuszach S, Peche LY, Konarev PV, Lamba D. A combined evolutionary and structural approach to disclose the primary structural determinants essential for proneurotrophins biological functions. Comput Struct Biotechnol J. (2021) May 7;19:2891-2904.
– Paoletti F, Merzel F, Cassetta A, Ogris I, Covaceuszach S, Grdadolnik J, Lamba D, Golič Grdadolnik S. Endogenous modulators of neurotrophin signaling: Landscape of the transient ATP-NGF interactions. Comput Struct Biotechnol J. (2021) May 7;19:2938-2949
– Paoletti F., de Chiara C., Kelly G., Covaceuszach S., Malerba F., Yan R., Lamba D., Cattaneo A., Pastore A. Conformational Rigidity within Plasticity Promotes Differential Target Recognition of Nerve Growth Factor. Front Mol Biosci. (2016) 3:83
– Covaceuszach S., Konarev P. V., Paoletti F., Krastanova I., Svergun D.I., Lamba D., Cattaneo A. “The conundrum of the high-affinity NGF binding site formation unveiled?”. Biophysical J. (2015) 108(3):687
