Solution structure of the carboxyl-terminal LIM domain from quail cysteine-rich protein CRP2
Solution structure of the carboxyl-terminal LIM domain from quail cysteine-rich protein CRP2
复制标题
DOI：
10.1074/jbc.272.18.12001
复制
发表时间：
1997-05-02
影响因子：
4.8
通讯作者：
Bister, K
中科院分区：
文献类型：
--
作者：
Konrat, R;Weiskirchen, R;Bister, K
富含半胱氨酸的蛋白 (CRP) 家族的蛋白（CRP1、CRP2 和 CRP3）参与与细胞分化和生长控制相关的多种过程，CRP 蛋白包含两个 LIM 结构域，每个结构域分别由 CCHC 和 CCCC 类型的两个锌结合模块形成。重组鹌鹑 CRP2 的羧基末端 LIM 结构域 (LIM2) 的溶液结构通过多维同核和异核磁共振波谱测定，折叠拓扑保留两个独立的锌结合模块（CCHC 和 CCCC），每个模块由两个正交排列的反平行 β 片层组成，羧基末端 CCCC 模块由 α 螺旋终止。 N-15 磁弛豫数据表明这些模块在构象灵活性方面有所不同。它们通过疏水核心区域堆积在一起。此外，CCHC模块中的Arg(122)和CCCC模块中的Glu(155)通过模块间氢键和/或盐桥连接。这些残基在 LIM 蛋白的 CRP 家族中绝对保守，它们的相互作用可能有助于 CRP LIM2 结构域中两个锌结合模块的相对方向。最近分析，鹌鹑 CRP2 LIM2 的整体折叠与相关但功能不同的 CRP 家族成员 CRP1 的羧基末端 LIM 结构域非常相似。羧基末端 CCCC 模块在结构上与红系转录因子 GATA-1 的 DNA 结合域相关。在鹌鹑CRP2 LIMB的两个锌结合模块中，由保守氨基酸残基组成的柔性环区位于LIM2结构域的同一侧，可能协同进行大分子识别。
Proteins of the cysteine-rich protein (CRP) family (CRP1, CRP2, and CRP3) are implicated in diverse processes linked to cellular differentiation and growth control, CRP proteins contain two LIM domains, each formed by two zinc-binding modules of the CCHC and CCCC type, respectively, The solution structure of the carboxyl-terminal LIM domain (LIM2) from recombinant quail CRP2 was determined by multidimensional homo- and heteronuclear magnetic resonance spectroscopy, The folding topology retains both independent zinc binding modules (CCHC and CCCC), Each module consists of two orthogonally arranged antiparallel beta-sheets, and the carboxyl-terminal CCCC module is terminated by an alpha-helix. N-15 magnetic relaxation data indicate that the modules differ in terms of conformational flexibility. They pack together via a hydrophobic core region. In addition, Arg(122) in the CCHC module and Glu(155) in the CCCC module are linked by an intermodular hydrogen bond and/or salt bridge. These residues are absolutely conserved in the CRP family of LIM proteins, and their interaction might contribute to the relative orientation of the two zinc-binding modules in CRP LIM2 domains, The global fold of quail CRP2 LIM2 is very similar to that of the carboxyl-terminal LIM domain of the related but functionally distinct CRP family member CRP1, analyzed recently. The carboxyl-terminal CCCC module is structurally related to the DNA-binding domain of the erythroid transcription factor GATA-1. In the two zinc-binding modules of quail CRP2 LIMB, flexible loop regions made up of conserved amino acid residues are located on the same side of the LIM2 domain and may cooperate in macromolecular recognition.