Characterization of the High-Affinity Fuzzy Complex between the Disordered Domain of the E7 Oncoprotein from High-Risk HPV and the TAZ2 Domain of CBP.
Characterization of the High-Affinity Fuzzy Complex between the Disordered Domain of the E7 Oncoprotein from High-Risk HPV and the TAZ2 Domain of CBP.
复制标题
DOI：
10.1021/acs.biochem.1c00669
复制
发表时间：
2021-12-28
期刊：
影响因子：
2.9
通讯作者：
Wright PE
中科院分区：
文献类型：
--
作者：
Risør MW;Jansma AL;Medici N;Thomas B;Dyson HJ;Wright PE
来自高危人乳头瘤病毒（HPV）株的E7蛋白的固有无序N-末端区域通过与许多细胞因子（包括转录共激活因子CREB结合蛋白（CBP）的TAZ 2结构域）相互作用而负责宿主细胞的致癌转化。使用各种光谱和生物化学工具，我们发现，尽管其纳摩尔亲和力，HPV 16 E7与TAZ 2的复合物是无序的和高度动态的。HPV 16 E7蛋白在TAZ 2表面上不采用单一构象，而是通过涉及两个保守基序（称为CR 1和CR2）的多重相互作用与其靶点杂乱地结合，这两个保守基序占据了TAZ 2上广泛的结合表面。该复合物的模糊性质反映了病毒蛋白的混杂结合库，其必须通过结合细胞环境中的多种宿主因子来有效地失调宿主细胞过程。
The intrinsically disordered N-terminal region of the E7 protein from high-risk human papillomavirus (HPV) strains is responsible for oncogenic transformation of host cells through its interaction with a number of cellular factors, including the TAZ2 domain of the transcriptional coactivator CREB-binding protein (CBP). Using a variety of spectroscopic and biochemical tools we find that, despite its nanomolar affinity, the HPV16 E7 complex with TAZ2 is disordered and highly dynamic. The HPV16 E7 protein does not adopt a single conformation on the surface of TAZ2 but engages promiscuously with its target through multiple interactions involving two conserved motifs, termed CR1 and CR2, that occupy an extensive binding surface on TAZ2. The fuzzy nature of the complex is a reflection of the promiscuous binding repertoire of viral proteins, which must efficiently dysregulate host cell processes by binding to a variety of host factors in the cellular environment.
登录
查看更多内容
DOI：
10.1073/pnas.89.10.4442
发表时间：
1992-05-15
影响因子：
11.1
作者：
HECK, DV;YEE, CL;MUNGER, K
通讯作者：
MUNGER, K
影响因子：
15
作者：
Arai, Munehito;Ferreon, Josephine C.;Wright, Peter E.
通讯作者：
Wright, Peter E.
DOI：
10.1073/pnas.1716098114
发表时间：
2017-11-14
影响因子：
11.1
作者：
Deshmukh, Lalit;Tugarinov, Vitali;Clore, G. Marius
通讯作者：
Clore, G. Marius
影响因子：
5.4
作者：
Chemes, Lucia B.;Sanchez, Ignacio E.;de Prat-Gay, Gonzalo
通讯作者：
de Prat-Gay, Gonzalo
影响因子：
4.6
作者：
Huang S;Umemoto R;Tamura Y;Kofuku Y;Uyeda TQ;Nishida N;Shimada I
通讯作者：
Shimada I