Research Explained: The Okur-Chung Neurodevelopmental Syndrome mutation CK2K198R leads to a rewiring of kinase specificity

Authors: Danielle Caefer, Nhat Phan, Jennifer Liddle, Jeremy Balsbaugh, Joseph O’Shea, Anastasios Tzingounis, Daniel Schwartz

Publication Date: April 19, 2022

Research Explained By: Brad Davidson, CSNK2A1 Foundation Science Communication Intern

Link to article: https://www.frontiersin.org/articles/10.3389/fmolb.2022.850661/full

Research Explained Summary: 

In this article, the researchers deeply characterized the effects of a mutation in the CSNK2A1 gene known as p.K198R. This mutation is the most prevalent mutation found in OCNDS to date. The CSNK2A1 gene encodes a component of the protein known as CK2, an enzyme that causes chemical reactions, generally acting on other proteins in what is known as a “signaling cascade” to modify their ability to perform subsequent functions such as cell growth. To act on its target proteins, CK2 must recognize these proteins. Proteins are comprised of subunits known as amino acids, and a specific string of amino acids in a row can be recognized by other proteins as sites for binding – this is how CK2 knows which proteins to modify. However, the authors of this paper found that the K198R mutation in CSNK2A1 changes the ability of CK2 to bind to sites on specific proteins that it normally acts on, instead biasing CK2 towards new binding sites on different proteins. The researchers then looked for proteins that the K198R mutant CK2 would act on but that the normal CK2 protein wouldn’t act on, indicating potential differences that could be leading to the symptoms seen in OCNDS. Previously, it was thought that this mutation generally decreased CK2 activity instead of changing what downstream proteins it targeted. Together, these results help inform the growing body of research regarding what the molecular function of common OCNDS mutations are so that eventually these differences can be targeted therapeutically.