Solution structure of the PWWP domain of the hepatoma-derived growth factor family
Solution structure of the PWWP domain of the hepatoma-derived growth factor family
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DOI：
10.1110/ps.04975305
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发表时间：
2005-03-01
期刊：
影响因子：
8
通讯作者：
Yokoyama, S
中科院分区：
文献类型：
--
作者：
Nameki, N;Tochio, N;Yokoyama, S
在众多的PWWP蛋白中，最大的同源蛋白群与肝癌衍生生长因子（HDGF）有关。HDGF和5种HDGF相关蛋白（HRPs）在其N末端的保守区域内都有一个PWWP结构域，PWWP结构域是许多染色质相关蛋白中的一个模块。在这项研究中，我们确定了HDGF-related protein-3（HRP-3）的PWWP结构域的溶液结构的NMR光谱。该结构由五链P-桶组成，其具有连接β 2和β 3的PWWP特异性长环（PR-环），随后是包括两个α-螺旋的螺旋区域。发现其结构具有特征性的溶剂暴露的疏水腔，其由β 1/β 2环（β-β弓）和β 3/β 4环中的大量芳香残基组成。在Tudor、染色体和MBT结构域中的相应位置处存在类似的配体结合腔，这些结构域与PWWP结构域具有结构和可能的进化关系。这些发现表明HDGF家族的PWWP结构域通过空腔与染色质的某些组分结合。
Among the many PWWP-containing proteins, the largest group of homologous proteins is related to hepatoma-derived growth factor (HDGF). Within a well-conserved region at the extreme N-terminus, HDGF and five HDGF-related proteins (HRPs) always have a PWWP domain, which is a module found in many chromatin-associated proteins. In this study, we determined the solution structure of the PWWP domain of HDGF-related protein-3 (HRP-3) by NMR spectroscopy. The structure consists of a five-stranded P-barrel with a PWWP-specific long loop connecting beta2 and beta3 (PR-loop), followed by a helical region including two a-helices. Its structure was found to have a characteristic solvent-exposed hydrophobic cavity, which is composed of an abundance of aromatic residues in the beta1/beta2 loop (beta-beta arch) and the beta3/beta4 loop. A similar ligand binding cavity occurs at the corresponding position in the Tudor, chromo, and MBT domains, which have structural and probable evolutionary relationships with PWWP domains. These findings suggest that the PWWP domains of the HDGF family bind to some component of chromatin via the cavity.