期刊
STRUCTURE
卷 28, 期 7, 页码 747-+出版社
CELL PRESS
DOI: 10.1016/j.str.2020.03.010
关键词
-
资金
- Swiss Light Source synchrotron (P. Scherrer Institute, Villigen, Switzerland)
- Ligue Contre le Cancer (Equipe Labellisee 2015)
- French Infrastructure for Integrated Structural Biology (FRISBI)
- Instruct-ERIC
- European Union (PDZnet network, Marie Sklodowska-Curie grant) [675341]
- Post-doctorants en France program of the Fondation ARC
- Russian Science Foundation [19-74-10031]
- Russian Science Foundation [19-74-10031] Funding Source: Russian Science Foundation
Protein-protein interaction motifs are often alterable by post-translational modifications. For example, 19% of predicted human PDZ domain-binding motifs (PBMs) have been experimentally proven to be phosphorylated, and up to 82% are theoretically phosphorylatable. Phosphorylation of PBMs may drastically rewire their interactomes, by altering their affinities for PDZ domains and 14-3-3 proteins. The effect of phosphorylation is often analyzed by performing phosphomimetic mutations. Here, we focused on the PBMs of HPV16-E6 viral oncoprotein and human RSK1 kinase. We measured the binding affinities of native, phosphorylated, and phosphomimetic variants of both PBMs toward the 266 human PDZ domains, We co-crystallized all the motif variants with a selected PDZ domain to characterize the structural consequence of the different modifications. Finally, we elucidated the structural basis of PBM capture by 14-3-3 proteins. This study provides novel atomic and interactomic insights into phosphorylatable dual specificity motifs and the differential effects of phosphorylation and phosphomimetic approaches.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据