Structural insights into specificity and diversity in mechanisms of ubiquitin recognition by ubiquitin-binding domains.
Structural insights into specificity and diversity in mechanisms of ubiquitin recognition by ubiquitin-binding domains.
复制标题
对泛素结合域识别泛素机制的特异性和多样性的结构见解。
DOI：
10.1042/bst20110729
复制
发表时间：
2012
影响因子：
3.9
通讯作者：
Searle MS
中科院分区：
文献类型：
--
作者：
Searle MS
UBD[Ub(泛素)结合域]是典型的50个残基的小蛋白基序，被受体蛋白用来在广泛的生物学过程中转导翻译后的Ub修饰，包括核转录因子B(κκB)信号转导和蛋白酶体降解途径。现在已有20多个UBD家族在结构细节上进行了表征，尽管许多家族识别Ub上典型的Ile44/Val70结合补丁，但有一小部分家族具有替代的Ub识别位点。ZNF216蛋白的A20锌指(A20样锌指)是后者的一种，它与Ub上以Asp58/Gln62为中心的一个极性部位有很高的亲和力。ZNF216与p62有一些共同的生物学功能，既与NF-κB信号激活有关，又作为蛋白酶体降解途径中的穿梭蛋白。P62的Uba结构域(Ub相关结构域)虽然通过Ile44/Val70补丁与Ub结合，但在形成稳定的二聚体方面是独一无二的，该二聚体对Ub的识别起负面调节作用。我们证明了A20Znf和Uba结构域能够通过与单个Ub分子独立的相互作用形成三元复合体，支持Ub作为中介多蛋白复合体组装和增强信号特异性的“枢纽”的功能模型。
UBDs [Ub (ubiquitin)-binding domains], which are typically small protein motifs of <50 residues, are used by receptor proteins to transduce post-translational Ub modifications in a wide range of biological processes, including NF-κB (nuclear factor κB) signalling and proteasomal degradation pathways. More than 20 families of UBDs have now been characterized in structural detail and, although many recognize the canonical Ile44/Val70-binding patch on Ub, a smaller number have alternative Ub-recognition sites. The A20 Znf (A20-like zinc finger) of the ZNF216 protein is one of the latter and binds with high affinity to a polar site on Ub centred around Asp58/Gln62. ZNF216 shares some biological function with p62, with both linked to NF-κB signal activation and as shuttle proteins in proteasomal degradation pathways. The UBA domain (Ub-associated domain) of p62, although binding to Ub through the Ile44/Val70patch, is unique in forming a stable dimer that negatively regulates Ub recognition. We show that the A20 Znf and UBA domain are able to form a ternary complex through independent interactions with a single Ub molecule, supporting functional models for Ub as a ‘hub’ for mediating multi-protein complex assembly and for enhancing signalling specificity.
登录
查看更多内容
影响因子：
5.6
作者：
Zhang, Daoning;Raasi, Shahri;Fushman, David
通讯作者：
Fushman, David
影响因子：
6.2
作者：
Najat, Dereen;Garner, Thomas;Layfield, Robert
通讯作者：
Layfield, Robert
影响因子：
5.6
作者：
Long, Jed;Garner, Thomas P.;Searle, Mark S.
通讯作者：
Searle, Mark S.
影响因子：
15
作者：
Liang, BY;Bushweller, JH;Tamm, LK
通讯作者：
Tamm, LK
影响因子：
16
作者：
Bomar MG;D'Souza S;Bienko M;Dikic I;Walker GC;Zhou P
通讯作者：
Zhou P