The role of a basic amino acid cluster in target site selection and non-specific binding of bZIP peptides to DNA.
The role of a basic amino acid cluster in target site selection and non-specific binding of bZIP peptides to DNA.
复制标题
碱性氨基酸簇在 bZIP 肽与 DNA 的靶位点选择和非特异性结合中的作用。
DOI：
10.1093/nar/25.15.2967
复制
发表时间：
1997
影响因子：
14.9
通讯作者：
Schepartz,A
中科院分区：
文献类型：
--
作者：
Metallo,SJ;Paolella,DN;Schepartz,A
转录因子在密切相关位点和大量非特异性DNA存在的情况下定位和结合其同源DNA位点的能力对细胞存活至关重要。CREB/ATF转录因子家族是一类重要的碱性区域亮氨酸拉链（bZIP）蛋白，对CRE位点具有高亲和力，对密切相关的AP-1位点具有低亲和力。CREB/ATF家族的成员在其bZIP元件的n端共享一个基本氨基酸簇。这个基本簇是引起CREB/ATF蛋白结合时CRE位点弯曲的必要和充分条件。利用来自人CREB - bp1 （CREB/ATF家族成员）和酵母GCN4的嵌合肽，研究了DNA弯曲和CRE/AP-1特异性在CREB/ATF蛋白中联系的可能性，GCN4缺乏基本簇和CRE/AP-1特异性。功能获得和功能丧失实验表明，基本簇不是所有特征CREB/ATF蛋白显示的CRE/AP-1特异性的原因。然而，基本簇负责对非特异性DNA诱导非常高的亲和力。结果进一步表明，含碱性团簇的多肽以随机螺旋形结合非特异性DNA。我们假设，高非特异性DNA亲和力的基本簇含肽是由于与磷酸主链的合作静电相互作用，不需要肽组织。
The ability of a transcription factor to locate and bind its cognate DNA site in the presence of closely related sites and a vast array of non-specific DNA is crucial for cell survival. The CREB/ATF family of transcription factors is an important group of basic region leucine zipper (bZIP) proteins that display high affinity for the CRE site and low affinity for the closely related AP-1 site. Members of the CREB/ATF family share in common a cluster of basic amino acids at the N-terminus of their bZIP element. This basic cluster is necessary and sufficient to cause the CRE site to bend upon binding of a CREB/ATF protein. The possibility that DNA bending and CRE/AP-1 specificity were linked in CREB/ATF proteins was investigated using chimeric peptides derived from human CRE-BP1 (a member of the CREB/ATF family) and yeast GCN4, which lacks both a basic cluster and CRE/AP-1 specificity. Gain of function and loss of function experiments demonstrated that the basic cluster was not responsible for the CRE/AP-1 specificity displayed by all characterized CREB/ATF proteins. The basic cluster was, however, responsible for inducing very high affinity for nonspecific DNA. It was further shown that basic clustercontaining peptides bind non-specific DNA in a random coil conformation. We postulate that the high nonspecific DNA affinities of basic cluster-containing peptides result from cooperative electrostatic interactions with the phosphate backbone that do not require peptide organization.
多种 bZIP 蛋白选择性 DNA 弯曲
影响因子：
5.3
作者：
T. Kerppola;T. Curran
通讯作者：
T. Curran