MPN+, a putative catalytic motif found in a subset of MPN domain proteins from eukaryotes and prokaryotes, is critical for Rpn11 function.
MPN+, a putative catalytic motif found in a subset of MPN domain proteins from eukaryotes and prokaryotes, is critical for Rpn11 function.
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DOI：
10.1186/1471-2091-3-28
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发表时间：
2002-09-20
期刊：
影响因子：
--
通讯作者：
Glickman MH
中科院分区：
文献类型：
--
作者：
Maytal-Kivity V;Reis N;Hofmann K;Glickman MH
三种大分子组合，即蛋白酶体的LID复合体、COP9-Signalosome(CSN)和eIF3复合体，都由含有MPN和PCI域的多个蛋白质组成。到目前为止，这些蛋白质中的任何一个都没有明确的特定功能，也没有阐明这些基序的重要性。尤其是Rpn11，一个LID亚基，作为含有MPN的蛋白质的范例，因为它高度保守，对蛋白酶体功能很重要。我们已经确定了一个序列基序，称为MPN+基序，它在MPN结构域蛋白的一个子集如Rpn11和Csn5/Jab1中高度保守，但不存在于这个亚家族之外。MPN+基序由5个极性残基组成，它们类似于水解酶类的活性部位残基，特别是金属蛋白酶的活性部位残基。通过定点突变，我们证明了MPN+残基对Rpn11的功能是重要的，而MPN+基序外的高度保守的Cys残基不是必需的。MPN+残基上的单一氨基酸替换都表现出相似的表型，包括生长缓慢，对温度和氨基酸类似物敏感，以及普遍的蛋白酶体依赖的蛋白降解缺陷。MPN+基序在某些MPN结构域蛋白中含量丰富，包括新发现的真核生物、细菌和古细菌的蛋白，这些蛋白被认为作用于传统的大型pCI/MPN复合体之外。MPN+基序的催化性质使其成为一个关键的酶功能的很好候选者，可能是与蛋白酶体相关的脱泛素化活性和与CSN相关的Nedd8/Rub1去除活性。
Three macromolecular assemblages, the lid complex of the proteasome, the COP9-Signalosome (CSN) and the eIF3 complex, all consist of multiple proteins harboring MPN and PCI domains. Up to now, no specific function for any of these proteins has been defined, nor has the importance of these motifs been elucidated. In particular Rpn11, a lid subunit, serves as the paradigm for MPN-containing proteins as it is highly conserved and important for proteasome function. We have identified a sequence motif, termed the MPN+ motif, which is highly conserved in a subset of MPN domain proteins such as Rpn11 and Csn5/Jab1, but is not present outside of this subfamily. The MPN+ motif consists of five polar residues that resemble the active site residues of hydrolytic enzyme classes, particularly that of metalloproteases. By using site-directed mutagenesis, we show that the MPN+ residues are important for the function of Rpn11, while a highly conserved Cys residue outside of the MPN+ motif is not essential. Single amino acid substitutions in MPN+ residues all show similar phenotypes, including slow growth, sensitivity to temperature and amino acid analogs, and general proteasome-dependent proteolysis defects. The MPN+ motif is abundant in certain MPN-domain proteins, including newly identified proteins of eukaryotes, bacteria and archaea thought to act outside of the traditional large PCI/MPN complexes. The putative catalytic nature of the MPN+ motif makes it a good candidate for a pivotal enzymatic function, possibly a proteasome-associated deubiquitinating activity and a CSN-associated Nedd8/Rub1-removing activity.
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DOI：
10.1073/pnas.89.22.10915
发表时间：
1992-11-15
影响因子：
11.1
作者：
HENIKOFF, S;HENIKOFF, JG
通讯作者：
HENIKOFF, JG
影响因子：
64.8
作者：
Gavin, AC;Bösche, M;Superti-Furga, G
通讯作者：
Superti-Furga, G
影响因子：
14.9
作者：
Bairoch, A;Apweller, R
通讯作者：
Apweller, R
影响因子：
4.8
作者：
JOHNSON, ES;MA, PCM;VARSHAVSKY, A
通讯作者：
VARSHAVSKY, A
DOI：
10.1038/80992
发表时间：
2000-11-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Groll, M;Bajorek, M;Finley, D
通讯作者：
Finley, D