Crystal structures of the tricorn interacting factor F3 from Thermoplasma acidophilum, a zinc aminopeptidase in three different conformations
Crystal structures of the tricorn interacting factor F3 from Thermoplasma acidophilum, a zinc aminopeptidase in three different conformations
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DOI：
10.1016/j.jmb.2005.03.070
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发表时间：
2005-06-17
影响因子：
5.6
通讯作者：
Brandstetter, H
中科院分区：
文献类型：
--
作者：
Kyrieleis, OJP;Goettig, P;Brandstetter, H
三角体相互作用因子F3是来自嗜酸热浆菌的89 kDa锌氨肽酶。F3与三角体相互作用因子F1和F2一起降解三角体蛋白酶产物，从而通过产生游离氨基酸完成蛋白酶体降解途径。在这里，我们提出了三种不同的构象在2.3埃分辨率的F3的晶体结构。锌氨肽酶由四个结构域组成：N-末端鞍状β-结构域;嗜热菌蛋白酶样催化结构域;小桶状β-结构域;和α-螺旋C-末端结构域，后者在活性位点形成深腔。三种晶体形式提供了F3的分子动力学的快照，其中C-末端结构域可以分别适应形成开放的、中间的和接近封闭的腔。F3具有保守的Zn 2+结合基序HEXXH和NEXFA以及N末端底物锚定谷氨酸残基，与白三烯A4水解酶一起代表了一种新型的谷锌素氨基蛋白酶亚家族。我们讨论了这些结构的功能方面的潜在的催化机制，底物识别和处理，以及可能的组件相互作用。(c)2005爱思唯尔有限公司保留所有权利。
The tricorn interacting factor F3 is an 89 kDa zinc aminopeptidase from the archaeon Thermoplasma acidophilum. Together with the tricorn interacting factors F1 and F2, F3 degrades the tricorn protease products and thus completes the proteasomal degradation pathway by generating free amino acids. Here, we present the crystal structures of F3 in three different conformations at 2.3 angstrom resolution. The zinc aminopeptidase is composed of four domains: an N-terminal saddle-like beta-structure domain; a thermolysin-like catalytic domain; a small barrel-like beta-structure domain; and an alpha-helical C-terminal domain, the latter forming a deep cavity at the active site. Three crystal forms provide snapshots of the molecular dynamics of F3 where the C-terminal domain can adapt to form an open, an intermediate and a nearly closed cavity, respectively. With the conserved Zn2+-binding motifs HEXXH and NEXFA as well as the N-terminal substrate-anchoring glutamate residues, F3 together with the leukotriene A4 hydrolase, represents a novel gluzincin subfamily of aminoproteases. We discuss the functional implications of these structures with respect to the underlying catalytic mechanism, substrate recognition and processing, and possible component interactions. (c) 2005 Elsevier Ltd. All rights reserved.