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SWI/SNF

维基百科,自由的百科全书
SWIB
拟南芥假定蛋白AT5G14170的SWIB/MDM2结构域的解析结构
鉴定
标志SWIB
PfamPF02201旧版
InterPro英语InterProIPR003121
SMART英语Simple Modular Architecture Research ToolSWIB
SCOP英语Structural Classification of Proteins1ycr / SUPFAM

分子生物学领域,SWI/SNF(英语:SWItch/Sucrose NonFermentable[1][2]是同时存在于真核生物原核生物中的一种核小体重塑复合物。简而言之,它们是一群与重塑DNA包装方式有关的蛋白质。SWI/SNF由多种蛋白构成,这些蛋白往往是SWI及SNF基因(SWI1SWI2/SNF2SWI3SWI5SWI6)的产物以及一些其它多肽[3]。SWI/SNF受DNA刺激后表现出ATP酶活性,利用ATP破坏并重塑核小体的组蛋白DNA之间相互作用的稳定性,不过这种结构改变的精确性质仍未明确。

人体中与SWI/SNF相似的蛋白是BAF(与SWI/SNF-A相似)和PBAF(与SWI/SNF-B相似)。BAF表示“BRG1英语SMARCA4HRBM英语SMARCA2相关因子”,PBAF则表示“聚溴相关的BAF”[4]

作用机理

人们发现酵母中的SWI/SNF复合物能使DNA在不同的位置与组蛋白结合成核小体[5]。目前已提出两种SWI/SNF重塑核小体的机制[6]。一种机制叫做“扭转扩散”,认为核小体DNA中的扭转缺陷发生单向扩散,使DNA从进入核小体的地方开始贴着组蛋白八聚体的表面螺旋状地传播。另一种机制叫做“突起”或“环再捕获”,意即DNA在核小体边缘与之分离,形成一环状突起。环状突起在组蛋白八聚体表面像波浪般传播,最后在核小体内部重新与之结合。这样DNA就在和组蛋白接触点数量不变的情况下完成位移[7]。最新研究提出了与“扭转扩散”机制相抵触的有力证据,使“环再捕获”模型更有说服力[8]

肿瘤抑制作用

人类的SWI/SNF复合物(mSWI/SNF)对很多人类恶性肿瘤有抑制作用。1998年首先发现它能抑制横纹肌样瘤(一种罕见的儿童恶性肿瘤)[9]。随着DNA测序成本逐渐降低,2010年左右许多肿瘤首次得到测序。其中数项研究表明SWI/SNF对多种恶性肿瘤有抑制作用[10][11][12][13]。对多个测序研究结果的荟萃分析表明,大约20%的人类恶性肿瘤中SWI/SNF存在变异[14]

SWIB/MDM2蛋白结构域

SWIB/MDM2蛋白结构域,全称是SWI/SNF复合物B/MDM2英语MDM2蛋白结构域是相当重要的蛋白结构域。这个蛋白结构域在SWI/SNF复合物B和p53肿瘤抑制蛋白的负向调节蛋白MDM2中均存在。已证明MDM2与SWIB复合物同源[15]

功能

SWIB/MDM2蛋白结构域的主要功能是协助基因表达。在酵母中,它表达BADH2英语betaine-aldehyde dehydrogenase、GAL1、GAL4和SUC2等数个基因。该蛋白结构域作用是促进基因转录。它有ATP酶的活性,能分解细胞基本能量“货币”单位ATP,放出能量以破坏DNA和组蛋白结合的稳定性,从而干扰染色质,并开放可供转录因子结合的位点,这就促进了基因的转录[16]

系列成员

以下列出酵母SWI/SNF系列基因成员以及人类相应的直系同源基因[17]

酵母 人类 功能
SWI1 ARID1A英语ARID1AARID1B英语ARID1B 含有LXXLL核受体结合基序
SWI2/SNF2 SMARCA4英语SMARCA4 ATP依赖的染色质重塑
SWI3 SMARCC1英语SMARCC1SMARCC2英语SMARCC2 功能未知的相似序列
SWP73 SMARCD1英语SMARCD1SMARCD2英语SMARCD2SMARCD3英语SMARCD3 功能未知的相似序列
SWP61 ACTL6A英语ACTL6AACTL6B英语ACTL6B 肌动蛋白样蛋白

历史

SWI/SNF首先发现于酿酒酵母Saccharomyces cerevisiae)中,以交替(switching,缩写SWI)型和不发酵蔗糖型(sucrose nonfermenting,缩写SNF)型交配后所得的酵母命名[16]

另见

参考文献 s

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