Brandstetter Hans, Kim Jeong-Sun, Groll Michael, Göttig Peter, Huber Robert
Abteilung Strukturforschung, Max-Planck-Institut für Biochemie, Martinsried, Germany.
Biol Chem. 2002 Jul-Aug;383(7-8):1157-65. doi: 10.1515/BC.2002.127.
Cell survival critically depends on the efficient use of available resources. This includes both the clearance and the recycling of those protein components that have become futile or defective. Several proteins sequentially accomplish this complex task. The proteasome serves as an initial protein shredder and generates peptides of 7-12 amino acids in length. In general, these products are useless burden to the cell and need further processing. A few years ago, a proteolytic system was identified in the model organism Thermoplasma acidophilum which indeed performs this processing [Tamura et al., Science 274 (1996), 1385-1389]. The hexameric core protein of this modular system, referred to as tricorn protease, is a 720 kDa protease which is able to assemble further into a giant icosahedral capsid, as determined by electron microscopy. Recently, we determined the crystal structure of the tricorn core particle at 2.0 A resolution [Brandstetter et al., Nature 414 (2001), 466-469]. Here we describe the structural and mechanistic basis for tricorn's processive degradation mode, including a novel electrostatic substrate-to-product sink, and suggest how further components might interact with the tricorn protease to complete the cellular waste recycling process.
细胞的存活严重依赖于对可用资源的有效利用。这包括对那些已变得无用或有缺陷的蛋白质成分的清除和再循环。几种蛋白质依次完成这项复杂的任务。蛋白酶体充当最初的蛋白质切碎机，产生长度为7至12个氨基酸的肽段。一般来说，这些产物对细胞是无用的负担，需要进一步处理。几年前，在模式生物嗜热栖热菌中鉴定出一种蛋白水解系统，它确实能进行这种处理 [田村等人，《科学》274 (1996)，1385 - 1389]。这个模块化系统的六聚体核心蛋白，被称为三触角蛋白酶，是一种720 kDa的蛋白酶，通过电子显微镜确定它能够进一步组装成一个巨大的二十面体衣壳。最近，我们以2.0 Å的分辨率确定了三触角核心颗粒的晶体结构 [布兰德施泰特等人，《自然》414 (2001)，466 - 469]。在这里，我们描述了三触角蛋白酶连续降解模式的结构和机制基础，包括一种新的从底物到产物的静电汇聚机制，并提出其他成分可能如何与三触角蛋白酶相互作用以完成细胞废物再循环过程。
