Structures of the lamin A/C R335W and E347K mutants: Implications for dilated cardiolaminopathies
Structures of the lamin A/C R335W and E347K mutants: Implications for dilated cardiolaminopathies
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DOI：
10.1016/j.bbrc.2011.12.136
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发表时间：
2012-02-10
影响因子：
3.1
通讯作者：
Bolognesi, Martino
中科院分区：
文献类型：
--
作者：
Bollati, Michela;Barbiroli, Alberto;Bolognesi, Martino
扩张型心肌病（DCM）是一种心肌的正常肌肉功能被特定或多种病因改变的疾病。大约25-35%的DCM患者表现出家族性疾病，大多数突变影响编码细胞骨架蛋白的基因。大多数DCM相关突变属于核纤层蛋白AC基因，特别是编码蛋白的Coil 2B结构域。在此背景下，我们集中我们的研究对两个核纤层蛋白Coil 2B结构域突变体（R335 W和E347 K）的晶体结构。R335和E347都是高度保守的残基，其取代对Coil 2B结构域的三维结构几乎没有影响;因此，我们可以假设突变可能干扰核纤层内组分或核因子的结合，这些组分或核因子已被提出与核纤层蛋白A/C相互作用/缔合。(C)2012 Elsevier Inc. All rights reserved.
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. (C) 2012 Elsevier Inc. All rights reserved.