Structures of the lamin A/C R335W and E347K mutants: Implications for dilated cardiolaminopathies

Journal Article · Fri Feb 10 04:00:00 EST 2012 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2011.12.136· OSTI ID:22207692

Bollati, Michela ^[1]; Barbiroli, Alberto ^[2]; Favalli, Valentina; Arbustini, Eloisa ^[3]; Charron, Philippe ^[4]; Bolognesi, Martino ^[1]

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1. Dipartimento di Scienze Biomolecolari e Biotecnologie and CIMAINA, Universita degli Studi di Milano, Via Celoria 26, 20133 Milano (Italy)
2. Sezione di Biochimica, Dipartimento di Scienze Molecolari Agroalimentari, Universita degli Studi di Milano, Via Celoria 2, 20133 Milano (Italy)
3. Centre for Inherited Cardiovascular Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia (Italy)
4. UPMC Univ Paris 6, AP-HP, Centre de Reference des Maladies Cardiaques Hereditaires, Hopital Pitie-Salpetriere, Paris (France)

Highlights: Black-Right-Pointing-Pointer Defects in the Lamin AC gene have been linked to more than 10 laminopathies. Black-Right-Pointing-Pointer R335 and E347 are highly conserved residues, whose mutation preserves Coil2B 3D structure. Black-Right-Pointing-Pointer R335W and E347K mutations may affect LMNA interaction with proteins of nuclear lamina. -- 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.

• OSTI ID: 22207692
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 418; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CRYSTAL STRUCTURE
DICHROISM
DISEASES
FILAMENTS
LIGHT SCATTERING
MUTANTS
MUTATIONS
MYOCARDIUM
PATIENTS
PROTEINS