Structural insights into the regulatory particle of the proteasome from Methanocaldococcus jannaschii.

Structural insights into the regulatory particle of the proteasome from Methanocaldococcus jannaschii.
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DOI:
10.1016/j.molcel.2009.04.021
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发表时间:
2009-05-14
期刊:
影响因子:
16
通讯作者:
Shi, Yigong
Shi, Yigong
中科院分区:
生物学1区
文献类型:
--
作者:
Zhang, Fan;Hu, Min;Tian, Geng;Zhang, Ping;Finley, Daniel;Jeffrey, Philip D.;Shi, Yigong

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真核蛋白酶体由降解未折叠蛋白的核心颗粒(CP)和负责多泛素化底物蛋白识别、atp依赖性展开和易位的调节颗粒(RP)组成。在jannaschii甲烷醛球菌中,RP是蛋白酶体激活核苷酸酶(PAN)的同六聚体复合体。在这里,我们报告了古细菌蛋白酶体的基本元素的晶体结构:CP, PAN的atp酶结构域,以及可能首先遇到底物的远端亚复合物。远端亚复合体包含一个线圈段和一个OB-fold结构域,这两个结构域似乎在真核蛋白酶体中是保守的。PAN的OB结构域形成一个具有13-Å孔的六聚环,这可能构成了底物易位通道的最外层收缩。这些研究揭示了完整蛋白酶体的结构代码和结构,确定了潜在的底物结合位点,并揭示了古细菌和真核生物RP中意想不到的不对称性。
Eukaryotic proteasome consists of a core particle (CP), which degrades unfolded protein, and a regulatory particle (RP), which is responsible for recognition, ATP-dependent unfolding and translocation of polyubiquitinated substrate protein. In the archaea Methanocaldococcus jannaschii, the RP is a homohexameric complex of proteasome-activating nucleotidase (PAN). Here we report the crystal structures of essential elements of the archaeal proteasome: the CP, the ATPase domain of PAN, and a distal subcomplex that is likely the first to encounter substrate. The distal subcomplex contains a coiled-coil segment and an OB-fold domain, both of which appear to be conserved in the eukaryotic proteasome. The OB domains of PAN form a hexameric ring with a 13-Å pore, which likely constitutes the outermost constriction of the substrate translocation channel. These studies reveal structural codes and architecture of the complete proteasome, identify potential substrate-binding sites, and uncover unexpected asymmetry in the RP of archaea and eukaryotes.
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