Multidisciplinary approach for the study of the proteins involved in the molecular mechanism of a rare disease such as Schwachman Diamond Syndrome.
Shwachman-Diamond syndrome is a rare disease that from a molecular point of view belongs to a class of diseases known as ribosomopathies. The two most involved proteins are SBDS and EFL1.
Shwachman-Diamond syndrome (SDS), a rare disease, first described in 1964, associates haematological defects with a dysmorphic syndrome characterized by lipomatosis of the pancreas, causing pancreatic insufficiency. SDS, from the point of view of the molecular mechanism, even if not yet fully clarified, belongs to a class of diseases known as ribosomopathies, linked to the alteration of the ribosome structure and / or its biogenesis. The two most involved proteins are SBDS and EFL1. The structural approach used / to be used are those of structural biology: crystallography, SAXS, cryo-EM, bioinformatics, and molecular dynamics simulations. Furthermore, we are exploring the possibility of finding small organic molecules capable of modulating the conformation of EFL1, both in the case of the lack of the contribution of the SBDS protein, due to its various mutations, and in the case of the mutations of the EFL1 protein.
– Delre, P., Alberga, D., Gijsbers, A., Sánchez-Puig, N., Nicolotti, O., Saviano, M., Siliqi, D., Mangiatordi, G.F. Exploring the role of elongation Factor-Like 1 (EFL1) in Shwachman-Diamond syndrome through molecular dynamics(2020) Journal of Biomolecular Structure and Dynamics, 38 (17), pp. 5219-5229. DOI: 10.1080/07391102.2019.1704883
– Gijsbers, A., Montagut, D.C., Méndez-Godoy, A., Altamura, D., Saviano, M., Siliqi, D., Sánchez-Puig, N. Interaction of the GTPase elongation factor like-1 with the shwachman-diamond syndrome protein and its missense mutations(2018) International Journal of Molecular Sciences, 19 (12), art. no. 4012. DOI: 10.3390/ijms19124012
– Siliqi, D., Foadi, J., Mazzorana, M., Altamura, D., Méndez-Godoy, A., Sánchez-Puig, N. Conformational flexibility of proteins involved in ribosome biogenesis: Investigations via small angle x-ray scattering (SAXS) 2018) Crystals, 8 (3), art. no. 109. DOI: 10.3390/cryst8030109
– Stepensky, P., Chacón-Flores, M., Kim, K.H., Abuzaitoun, O., Bautista-Santos, A., Simanovsky, N., Siliqi, D., Altamura, D., Méndez-Godoy, A., Gijsbers, A., Eddin, A.N., Dor, T., Charrow, J., Sánchez-Puig, N., Elpeleg, O. Mutations in EFL1, an SBDS partner, are associated with infantile pancytopenia, exocrine pancreatic insufficiency and skeletal anomalies in a Shwachman-Diamond like syndrome(2017) Journal of Medical Genetics, 54 (8), pp. 558-566. DOI: 10.1136/jmedgenet-2016-104366
