Dimeric structure of p300/CBP associated factor.

Dimeric structure of p300/CBP associated factor.
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p300/CBP 相关因子的二聚体结构

DOI:
10.1186/1472-6807-14-2
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发表时间:
2014-01-14
影响因子:
--
通讯作者:
Han A
Han A
中科院分区:
生物4区
文献类型:
--
作者:
Shi S;Lin J;Cai Y;Yu J;Hong H;Ji K;Downey JS;Lu X;Chen R;Han J;Han A

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p300/CBP相关因子(PCAF,也称为赖氨酸乙酰转移酶2B的KAT2B)是megadalton后生动物复合体ATAC (Ada-Two-A - containing complex)的催化亚基,用于组蛋白乙酰化。然而,关于PCAF酶活性的调控,人们所知相对较少。结果我们得到了PCAF乙酰转移酶(HAT)结构域的两种二聚体结构。这些二聚化是由四螺旋疏水相互作用或ß-sheet扩展介导的。我们的化学交联实验结合定点诱变表明,PCAF HAT结构域主要通过其中一个观察到的界面在溶液中形成二聚体。麦芽糖结合蛋白(maltose binding protein, MBP)-pull - down、共免疫沉淀和多角度静态光散射实验结果进一步表明PCAF二聚体状态是可检测到的,并且可能存在于体内。综上所述,我们的结构和生化研究表明PCAF似乎是其功能ATAC复合物的二聚体。
Backgroundp300/CBP associating factor (PCAF, also known as KAT2B for lysine acetyltransferase 2B) is a catalytic subunit of megadalton metazoan complex ATAC (Ada-Two-A containing complex) for acetylation of histones. However, relatively little is known about the regulation of the enzymatic activity of PCAF.ResultsHere we present two dimeric structures of the PCAF acetyltransferase (HAT) domain. These dimerizations are mediated by either four-helical hydrophobic interactions or a ß-sheet extension. Our chemical cross-linking experiments in combined with site-directed mutagenesis demonstrated that the PCAF HAT domain mainly forms a dimer in solution through one of the observed interfaces. The results of maltose binding protein (MBP)-pulldown, co-immunoprecipitation and multiangle static light scattering experiments further indicated that PCAF dimeric state is detectable and may possibly exist in vivo.ConclusionsTaken together, our structural and biochemical studies indicate that PCAF appears to be a dimer in its functional ATAC complex.
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