Qian Chengmin, Zhang Qiang, Li SiDe, Zeng Lei, Walsh Martin J, Zhou Ming-Ming
Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, One Gustave L. Levy Place, New York, New York 10029, USA.
Nat Struct Mol Biol. 2005 Dec;12(12):1078-85. doi: 10.1038/nsmb1022. Epub 2005 Nov 20.
The evolutionarily conserved Swi3p, Rsc8p and Moira (SWIRM) domain is found in many chromosomal proteins involved in chromatin modifications or remodeling. Here we report the three-dimensional solution structure of the SWIRM domain from the human transcriptional adaptor ADA2alpha. The structure reveals a five-helix bundle consisting of two helix-turn-helix motifs connected by a central long helix, reminiscent of the histone fold. Using structural and biochemical analyses, we showed that the SWIRM domains of human ADA2alpha and SMARC2 bind to double-stranded and nucleosomal DNA, and we identified amino acid residues required for this function. We demonstrated that the ADA2alpha SWIRM domain is colocalized with lysine-acetylated histone H3 in the cell nucleus and that it potentiates the ACF remodeling activity by enhancing accessibility of nucleosomal linker DNA bound to histone H1. These data suggest a functional role of the SWIRM domain in chromatin remodeling.
进化上保守的Swi3p、Rsc8p和Moira（SWIRM）结构域存在于许多参与染色质修饰或重塑的染色体蛋白中。在此，我们报道了人类转录衔接子ADA2α的SWIRM结构域的三维溶液结构。该结构揭示了一个由两个螺旋-转角-螺旋基序通过一个中央长螺旋连接而成的五螺旋束，让人联想到组蛋白折叠。通过结构和生化分析，我们表明人类ADA2α和SMARC2的SWIRM结构域与双链和核小体DNA结合，并鉴定了该功能所需的氨基酸残基。我们证明ADA2α的SWIRM结构域在细胞核中与赖氨酸乙酰化的组蛋白H3共定位，并且它通过增强与组蛋白H1结合的核小体连接DNA的可及性来增强ACF重塑活性。这些数据表明SWIRM结构域在染色质重塑中具有功能作用。
