人类Josephin-2活性和调控的结构见解

IF 3.5 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Kimberly C. Grasty, Stephen D. Weeks , Patrick J. Loll
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引用次数: 10

摘要

人去泛素化酶MJD家族包含四个成员:Ataxin-3、Ataxin-3样蛋白(AT3L)、Josephin-1和Josephin-2。它们都有一个保守的催化单元,称为约瑟夫结构域。Ataxin-3和AT3L也包含广泛的调节其功能的调控区域,而Josephin -1和-2则要小得多,只包含Josephin结构域。为了深入了解这些最小的josephin与较大的josephin有何不同,我们确定了人类Josephin-2的2.3 Å x射线晶体结构,并探测了该酶的底物特异性。在结构中可以看到几个大的无序环,表明这是一种高度动态的酶。Josephin-2缺乏在ataxin-3中发现的几个变构位点,但其结构表明可能通过邻近活性位点的环的泛素化进行调节。该酶优先识别含有K11、K48和K63键的底物,这表明它可能在维持蛋白质质量控制中起作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Structural insights into the activity and regulation of human Josephin-2

Structural insights into the activity and regulation of human Josephin-2

The MJD family of human deubiquitinating enzymes contains four members: Ataxin-3, the ataxin-3-like protein (AT3L), Josephin-1, and Josephin-2. All share a conserved catalytic unit known as the Josephin domain. Ataxin-3 and AT3L also contain extensive regulatory regions that modulate their functions, whereas Josephins-1 and -2 are substantially smaller, containing only the Josephin domain. To gain insight into how these minimal Josephins differ from their larger relatives, we determined the 2.3 Å X-ray crystal structure of human Josephin-2 and probed the enzyme’s substrate specificity. Several large disordered loops are seen in the structure, suggesting a highly dynamic enzyme. Josephin-2 lacks several allosteric sites found in ataxin-3, but its structure suggests potential regulation via ubiquitination of a loop adjoining the active site. The enzyme preferentially recognizes substrates containing K11, K48, and K63 linkages, pointing toward a possible role in maintenance of protein quality control.

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来源期刊
Journal of Structural Biology: X
Journal of Structural Biology: X Biochemistry, Genetics and Molecular Biology-Structural Biology
CiteScore
6.50
自引率
0.00%
发文量
20
审稿时长
62 days
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