TY - JOUR
T1 - Structures of the lamin A/C R335W and E347K mutants
T2 - Implications for dilated cardiolaminopathies
AU - Bollati, Michela
AU - Barbiroli, Alberto
AU - Favalli, Valentina
AU - Arbustini, Eloisa
AU - Charron, Philippe
AU - Bolognesi, Martino
PY - 2012/2/10
Y1 - 2012/2/10
N2 - 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.
AB - 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.
KW - Coiled coil
KW - Crystal structure
KW - Dilated cardiomyopathy
KW - Laminopathy
KW - Nuclear lamins
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U2 - 10.1016/j.bbrc.2011.12.136
DO - 10.1016/j.bbrc.2011.12.136
M3 - Article
C2 - 22266370
AN - SCOPUS:84856657199
VL - 418
SP - 217
EP - 221
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -