The crystal structure of the carboxy-terminal dimerization domain of htpG, the Escherichia coli Hsp90, reveals a potential substrate binding site
The crystal structure of the carboxy-terminal dimerization domain of htpG, the Escherichia coli Hsp90, reveals a potential substrate binding site
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DOI：
10.1016/j.str.2004.03.020
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发表时间：
2004-06-01
期刊：
影响因子：
5.7
通讯作者：
Agard, DA
中科院分区：
文献类型：
--
作者：
Harris, SF;Shiau, AK;Agard, DA
热休克蛋白90是一种普遍存在的、高度保守的分子伴侣，参与多种蛋白质的折叠和稳定。除了其一般蛋白质折叠的能力之外，Hsp 90还影响着关键生物学和疾病过程的多种细胞信号传导途径。已经提出Hsp 90作为分子钳发挥功能，通过其羧基末端结构域二聚化，并利用ATP结合和水解来驱动大的构象变化，包括氨基末端和中间结构域的瞬时二聚化。我们已经确定了htpG，大肠杆菌Hsp 90的羧基末端结构域的2.6埃的X-射线晶体结构。这种结构揭示了一种新的折叠，二聚化依赖于四螺旋束的形成。值得注意的是，在螺旋二聚化基序的近端，每个单体将短螺旋投射到溶剂中。该螺旋的位置、灵活性和两亲性特征表明，它可能在底物结合中起作用，因此具有分子伴侣活性。
Hsp90 is a ubiquitous, well-conserved molecular chaperone involved in the folding and stabilization of diverse proteins. Beyond its capacity for general protein folding, Hsp90 influences a wide array of cellular signaling pathways that underlie key biological and disease processes. It has been proposed that Hsp90 functions as a molecular clamp, dimerizing through its carboxy-terminal domain and utilizing ATP binding and hydrolysis to drive large conformational changes including transient dimerization of the amino-terminal and middle domains. We have determined the 2.6 Angstrom X-ray crystal structure of the carboxy-terminal domain of htpG, the Escherichia coli Hsp90. This structure reveals a novel fold and that dimerization is dependent upon the formation of a four-helix bundle. Remarkably, proximal to the helical dimerization motif, each monomer projects a short helix into solvent. The location, flexibility, and amphipathic character of this helix suggests that it may play a role in substrate binding and hence chaperone activity.