title: Structures of the lamin A/C R335W and E347K mutants: implications for dilated cardiolaminopathies.
abstract: Dilated cardiomyopathy (DCM) is a condition whereby the normal muscular function of the myocardium is altered by specific or multiple aetiologies. About 25-35% of DCM patients show familial forms of the disease, with most mutations affecting genes encoding cytoskeletal proteins. Most of the DCM-related mutations fall in the Lamin AC gene, in particular in the Coil2B domain of the encoded protein. In this context, we focussed our studies on the crystal structures of two lamin Coil2B domain mutants (R335W and E347K). Both R335 and E347 are higly conserved residues whose substitution has little effects on the Coil2B domain three-dimensional structure; we can thus hypothesize that the mutations may interfere with the binding of components within the nuclear lamina, or of nuclear factors, that have been proposed to interact/associate with lamin A/C.
authors.affiliation: Dipartimento di Scienze Biomolecolari e Biotecnologie and CIMAINA, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Bollati
authors.forename: Alberto
authors.initials: A
authors.lastname: Barbiroli
authors.forename: Valentina
authors.initials: V
authors.lastname: Favalli
authors.forename: Eloisa
authors.initials: E
authors.lastname: Arbustini
authors.forename: Philippe
authors.initials: P
authors.lastname: Charron
authors.forename: Martino
authors.initials: M
authors.lastname: Bolognesi
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D018360:Crystallography, X-Ray; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D009154:Mutation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A