4.6 Review

From structure to the dynamic regulation of a molecular switch: A journey over 3 decades

期刊

JOURNAL OF BIOLOGICAL CHEMISTRY
卷 296, 期 -, 页码 -

出版社

ELSEVIER
DOI: 10.1016/j.jbc.2021.100746

关键词

-

向作者/读者索取更多资源

The Protein Data Bank has played a crucial role in the signaling community for over 30 years, facilitating information sharing between academics and industry. Through the study of protein kinases, particularly cAMP-dependent protein kinase, researchers have made significant discoveries including the importance of crystal packing in biological processes and disease relevance. Integrating crystallography with other techniques is opening up new possibilities for understanding intrinsically disordered regions and dynamic biological processes.
It is difficult to imagine where the signaling community would be today without the Protein Data Bank. This visionary resource, established in the 1970s, has been an essential partner for sharing information between academics and industry for over 3 decades. We describe here the history of our journey with the protein kinases using cAMP-dependent protein kinase as a prototype. We summarize what we have learned since the first structure, published in 1991, why our journey is still ongoing, and why it has been essential to share our structural information. For regulation of kinase activity, we focus on the cAMP-binding protein kinase regulatory subunits. By exploring full-length macromolecular complexes, we discovered not only allostery but also an essential motif originally attributed to crystal packing. Massive genomic data on disease mutations allows us to now revisit crystal packing as a treasure chest of possible protein:protein interfaces where the biological significance and disease relevance can be validated. It provides a new window into exploring dynamic intrinsically disordered regions that previously were deleted, ignored, or attributed to crystal packing. Merging of crystallography with cryo-electron microscopy, cryo-electron tomography, NMR, and millisecond molecular dynamics simulations is opening a new world for the signaling community where those structure coordinates, deposited in the Protein Data Bank, are just a starting point!

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。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据