Riccardo Tortarolo
Conformational Dynamics and Molecular Characterization of MORN motifs to shed light on homophilic interactions driving the formation of protein macromolecular superassemblies.
Rel. Marco Agostino Deriu, Marcello Miceli. Politecnico di Torino, Corso di laurea magistrale in Ingegneria Biomedica, 2021
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Abstract
Membrane Occupation Recognition Nexus (MORN) motifs are protein domains poorly characterized despite the fact of being widely diffuse among different species in both eucaryotic and procaryotic organisms. These motifs are characterized by several repetitions of an highly conserved β-harpins modules. Experimental evidence is often conflicting showing a possible lipids binding activity as well as a protein-protein interaction capability. In mammalian MORN repetitions are found in Alsin, a multiple domain protein of 1657 amino acids transcripted from Amyotrophic Lateral Sclerosis type 2 (ALS2) gene, whose mutations are associated with Infantile-onset Ascending Hereditary Spastic Paralysis (IAHSP) disease. IAHSP is a rare neurodegenerative condition whose symptoms start to occur from the first years of life manifesting lower limbs spasticity and usually worsening also affecting the upper limbs and reaching tetraplegia.
Literature evidence suggest that ALS2 MORN domains are involved in homophilic interactions to form an Alsin tetrameric form and binding activity of the guanosine triphosphatase Rab5
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