基础转录机制中的新型锌指基序：转录延伸因子TFIIS核酸结合结构域的三维核磁共振研究

Novel zinc finger motif in the basal transcriptional machinery: three-dimensional NMR studies of the nucleic acid binding domain of transcriptional elongation factor TFIIS.

作者信息

Qian X, Gozani S N, Yoon H, Jeon C J, Agarwal K, Weiss M A

机构信息

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.

出版信息

Biochemistry. 1993 Sep 28;32(38):9944-59. doi: 10.1021/bi00089a010.

DOI:10.1021/bi00089a010

PMID:8399164

Abstract

Transcriptional elongation provides a key control point in the regulation of eukaryotic gene expression. Here we describe homonuclear and 15N-heteronuclear 3D NMR studies of the nucleic acid binding domain of human transcriptional elongation factor TFIIS. This domain contains a Cys4 Zn(2+)-binding site with no homology to previously characterized Cys4, Cys6, or Cys2-His2 Zn fingers. Complete 1H and 15N NMR resonance assignment of a 50-residue TFIIS peptide-Zn2+ complex is obtained. Its solution structure, as determined by distance geometry/simulated annealing (DG/SA) calculations, exhibits a novel three-stranded antiparallel beta-sheet (designated the Zn ribbon). Analogous sequence motifs occur in a wide class of proteins involved in RNA or DNA transactions, including human basal transcriptional initiation factor TFIIE. A three-dimensional model of the TFIIE Cys4 domain is obtained by DG-based homology modeling. The role of the TFIIS Zn ribbon in the control of eukaryotic transcriptional elongation is discussed.

摘要

转录延伸是真核基因表达调控中的一个关键控制点。在此，我们描述了人类转录延伸因子TFIIS核酸结合结构域的同核和15N异核3D NMR研究。该结构域包含一个Cys4 Zn(2+)结合位点，与先前鉴定的Cys4、Cys6或Cys2-His2锌指无同源性。获得了一个50个残基的TFIIS肽-Zn2+复合物的完整1H和15N NMR共振归属。通过距离几何/模拟退火（DG/SA）计算确定的其溶液结构呈现出一种新型的三链反平行β-折叠（称为锌带）。类似的序列基序存在于广泛的参与RNA或DNA事务的蛋白质中，包括人类基础转录起始因子TFIIE。通过基于DG的同源建模获得了TFIIE Cys4结构域的三维模型。讨论了TFIIS锌带在真核转录延伸控制中的作用。