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HDAC6 ZnF UBP as the Modifier of Tau Structure and Function
Biochemistry ( IF 2.9 ) Pub Date : 2020-11-25 , DOI: 10.1021/acs.biochem.0c00585
Abhishek Ankur Balmik 1, 2 , Hariharakrishnan Chidambaram 1, 2 , Abha Dangi 2, 3 , Udaya Kiran Marelli 2, 3 , Subashchandrabose Chinnathambi 1, 2
Affiliation  

Histone deacetylase 6 is a class II histone deacetylase primarily present in the cytoplasm and involved in the regulation of various cellular functions. It consists of two catalytic deacetylase domains and a unique zinc finger ubiquitin binding protein domain, which sets it apart from other HDACs. HDAC6 is known to regulate cellular activities by modifying the function of microtubules, HSP90, and cortactin through deacetylation. Apart from the catalytic activity of HDAC6, it interacts with other proteins through either the SE14 domain or the ZnF UBP domain to modulate their functions. Here, we have studied the role of the HDAC6 ZnF UBP domain as a modifier of Tau aggregation by its direct interaction with the polyproline region/repeat region of Tau. Interaction of HDAC6 ZnF UBP with Tau was found to reduce the propensity of Tau to self-aggregate and to disaggregate preformed aggregates in a concentration-dependent manner and also bring about the conformational changes in Tau protein. The interaction of HDAC6 ZnF UBP with Tau results in its degradation, suggesting either proteolytic activity of HDAC6 ZnF UBP or its role in enhancing autoproteolysis of Tau.

中文翻译:

HDAC6 ZnF UBP作为Tau结构和功能的修饰剂

组蛋白脱乙酰基酶6是II类组蛋白脱乙酰基酶,主要存在于细胞质中,参与各种细胞功能的调节。它由两个催化脱乙酰酶结构域和一个独特的锌指泛素结合蛋白结构域组成,这使其与其他HDAC脱颖而出。已知HDAC6通过脱乙酰基修饰微管,HSP90和皮质激素的功能来调节细胞活性。HDAC6除了具有催化活性外,还通过SE14结构域或ZnF UBP结构域与其他蛋白质相互作用,以调节其功能。在这里,我们研究了HDAC6 ZnF UBP结构域作为Tau聚集修饰剂的作用,因为它与Tau的聚脯氨酸区域/重复区域直接相互作用。发现HDAC6 ZnF UBP与Tau的相互作用降低了Tau自聚集的倾向,并以浓度依赖性的方式分解了预先形成的聚集体,还引起了Tau蛋白的构象变化。HDAC6 ZnF UBP与Tau的相互作用导致其降解,表明HDAC6 ZnF UBP的蛋白水解活性或其在增强Tau自蛋白水解中的作用。
更新日期:2020-12-08
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