Molecular analysis of the prokaryotic ubiquitin-like protein (Pup) conjugation pathway in Mycobacterium tuberculosis.
Molecular analysis of the prokaryotic ubiquitin-like protein (Pup) conjugation pathway in Mycobacterium tuberculosis.
复制标题
DOI：
10.1111/j.1365-2958.2010.07276.x
复制
发表时间：
2010-09
影响因子：
3.6
通讯作者：
Darwin KH
中科院分区：
文献类型：
--
作者：
Cerda-Maira FA;Pearce MJ;Fuortes M;Bishai WR;Hubbard SR;Darwin KH
被分枝杆菌蛋白酶体降解的蛋白质被原核泛素样蛋白（Pup）标记，Pup是一种64个残基的内在无序蛋白质。在一个被称为“pupylation”的过程中，Pup是用末端谷氨酰胺合成的，其在通过PafA（蛋白酶体辅助因子A）连接到底物赖氨酸之前通过Dop（Pup的脱酰胺酶）脱酰胺成谷氨酸。重要的是，PafA以前被证明是必不可少的，导致致命的感染结核分枝杆菌（Mtb）在小鼠中。在这项研究中，我们表明，Dop，如PafA，是结核分枝杆菌的全部毒力所需的。此外，我们表明Dop不仅参与Pup的脱酰胺，而且还需要维持Mtb中的野生型稳态pupylated蛋白水平。最后，使用结构模型和定点突变，我们的数据表明Dop和PafA是谷氨酰胺合成酶折叠蛋白质家族的成员。
Proteins targeted for degradation by the Mycobacterium proteasome are post-translationally tagged with prokaryotic ubiquitin-like protein (Pup), an intrinsically disordered protein of 64 residues. In a process termed “pupylation”, Pup is synthesized with a terminal glutamine, which is deamidated to glutamate by Dop (deamidase of Pup) prior to attachment to substrate lysines by PafA (proteasome accessory factor A). Importantly, PafA was previously shown to be essential to cause lethal infections by Mycobacterium tuberculosis (Mtb) in mice. In this study we show that Dop, like PafA, is required for the full virulence of Mtb. Additionally, we show that Dop is involved not only in the deamidation of Pup, but is also needed to maintain wild type steady state levels of pupylated proteins in Mtb. Finally, using structural models and site-directed mutagenesis our data suggest Dop and PafA are members of the glutamine synthetase fold family of proteins.
登录
查看更多内容
影响因子：
3.6
作者：
Geissler B;Bonebrake A;Sheahan KL;Walker ME;Satchell KJ
通讯作者：
Satchell KJ
影响因子：
56.9
作者：
Darwin, KH;Ehrt, S;Nathan, CF
通讯作者：
Nathan, CF
影响因子：
82.9
作者：
Gandotra, Sheetal;Schnappinger, Dirk;Ehrt, Sabine
通讯作者：
Ehrt, Sabine
结核分枝杆菌的核酸泛素样蛋白（PUP）蛋白质组[校正]。
影响因子：
3.7
作者：
Festa RA;McAllister F;Pearce MJ;Mintseris J;Burns KE;Gygi SP;Darwin KH
通讯作者：
Darwin KH
影响因子：
16.8
作者：
Striebel, Frank;Imkamp, Frank;Weber-Ban, Eilika
通讯作者：
Weber-Ban, Eilika