Α-辅肌动蛋白2 - 维基百科,自由的百科全书
α-辅肌动蛋白2(英語:Alpha-actinin-2)是一种蛋白质,在人类中由ACTN2基因编码。[6]该基因编码一种在骨骼肌和心肌中表达的α-辅肌动蛋白异构体,其功能是将肌原纤维肌动蛋白细丝和肌联蛋白锚定到Z盘上。
结构
[编辑]α-辅肌动蛋白2是一种103.8kDa的蛋白质,由894个氨基酸组成。[7][8]每个分子都是棒状的(长度为35nm),并且以反平行的方式同源二聚化。每个单体都有一个N端肌动蛋白结合区,由两个钙调理蛋白同源结构域、两个C端EF手结构域和四个串联血影蛋白样重复序列组成,形成分子中心区域的杆状结构域。[9] 人类α-辅肌动蛋白2在3.5Å处的高分辨率晶体结构最近得到解决。[10]α辅肌动蛋白属于血影蛋白基因超家族,它代表一组不同的肌动蛋白结合细胞骨架蛋白,包括血影蛋白、抗肌萎缩蛋白、肌营养相关蛋白和丝束蛋白。[9]骨骼肌、心脏和平滑肌亚型定位于Z盘和类似的致密体,它们有助于锚定肌原纤维肌动蛋白丝。α-肌动蛋白2已被证明与KCNA5、[11][12]DLG1、[11]DISC1、[13]MYOZ1、[14]GRIN2B、[15]ADAM12、[16]ACTN3、[17]MYPN、[18]PDLIM3、[19]PKN、[20]MYOT、[21]TTN、[22]NMDAR、[23]SYNPO2、[24]LDB3、[25]和MYOZ1[14]产生相互作用。
功能
[编辑]α-辅肌动蛋白2的主要功能是在Z盘上交联丝状肌动蛋白分子和来自相邻肌小节的肌联蛋白分子,该功能受磷脂调节。[26][27]从汉普顿等人的研究中可以清楚地看出,这种交联可以呈现多种构象,偏好60°和120°的角度。[28]α-辅肌动蛋白2还在Z盘上的对接信号分子中发挥作用,另外的研究还表明α-辅肌动蛋白2与心脏离子通道的结合有关,尤其是Kv1.5。[11]
临床意义
[编辑]ACTN2的突变与肥厚型心肌病、[29]扩张型心肌病和心内膜弹力纤维增生症有关。[30]α-辅肌动蛋白2的不同功能反映在携带ACTN2突变的患者的不同临床表现中。[31]
参考资料
[编辑]- ^ 與Α-辅肌动蛋白2相關的疾病;在維基數據上查看/編輯參考.
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延申阅读
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- Mukai H, Toshimori M, Shibata H, Takanaga H, Kitagawa M, Miyahara M, Shimakawa M, Ono Y. Interaction of PKN with alpha-actinin. The Journal of Biological Chemistry. February 1997, 272 (8): 4740–6. PMID 9030526. doi:10.1074/jbc.272.8.4740
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.
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.
外部链接
[编辑]- Mass spectrometry characterization of human ACTN2 at COPaKB
- GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview (页面存档备份,存于互联网档案馆)
- Human ACTN2 genome location and ACTN2 gene details page in the UCSC Genome Browser.
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