Allosteric regulation of deubiquitylase activity through ubiquitination.
Allosteric regulation of deubiquitylase activity through ubiquitination.
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通过泛素化对去泛素酶活性的变构调节。
DOI：
10.3389/fmolb.2015.00002
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发表时间：
2015
影响因子：
5
通讯作者：
Pastore A
中科院分区：
文献类型：
--
作者：
Faggiano S;Menon RP;Kelly GP;Todi SV;Scaglione KM;Konarev PV;Svergun DI;Paulson HL;Pastore A
Ataxin-3是一种半胱氨酸蛋白酶，可特异性切割多泛素链并参与泛素蛋白酶体途径，是脊髓小脑性共济失调3型的蛋白。酶活性驻留在n端Josephin结构域。ataxin-3的一个不寻常的特征是它的低酶活性，特别是对单泛素化底物和短泛素链。然而，Josephin结构域赖氨酸117的特异性泛素化通过未知的机制激活了ataxin-3。在这里，我们研究了K117泛素化对蛋白结构和酶活性的影响。我们发现共价连接的泛素依赖于Josephin结构域，形成一个紧凑的球形片段，并占据一个泛素结合位点，该位点以前被认为是对底物识别必不可少的。在这样做时，泛素化通过将酶锁定在激活状态来增强酶的活性。我们的研究结果表明，泛素既是一个底物，也是一个变构调节因子。我们提供了一个新的例子，其中构象开关控制介导去泛素化的酶的活性。
Ataxin-3, the protein responsible for spinocerebellar ataxia type-3, is a cysteine protease that specifically cleaves poly-ubiquitin chains and participates in the ubiquitin proteasome pathway. The enzymatic activity resides in the N-terminal Josephin domain. An unusual feature of ataxin-3 is its low enzymatic activity especially for mono-ubiquitinated substrates and short ubiquitin chains. However, specific ubiquitination at lysine 117 in the Josephin domain activates ataxin-3 through an unknown mechanism. Here, we investigate the effects of K117 ubiquitination on the structure and enzymatic activity of the protein. We show that covalently linked ubiquitin rests on the Josephin domain, forming a compact globular moiety and occupying a ubiquitin binding site previously thought to be essential for substrate recognition. In doing so, ubiquitination enhances enzymatic activity by locking the enzyme in an activated state. Our results indicate that ubiquitin functions both as a substrate and as an allosteric regulatory factor. We provide a novel example in which a conformational switch controls the activity of an enzyme that mediates deubiquitination.
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影响因子：
3.4
作者：
Durcan TM;Fon EA
通讯作者：
Fon EA
影响因子：
64.5
作者：
Duda, David M.;Borg, Laura A.;Scott, Daniel C.;Hunt, Harold W.;Hammel, Michal;Schulman, Brenda A.
通讯作者：
Schulman, Brenda A.
影响因子：
3.5
作者：
Masino, L;Musi, V;Pastore, A
通讯作者：
Pastore, A
影响因子：
16.6
作者：
Blount, Jessica R.;Tsou, Wei-Ling;Ristic, Gorica;Burr, Aaron A.;Ouyang, Michelle;Galante, Holland;Scaglione, K. Matthew;Todi, Sokol V.
通讯作者：
Todi, Sokol V.
影响因子：
6.1
作者：
Konarev, PV;Volkov, VV;Svergun, DI
通讯作者：
Svergun, DI