Structural Studies and Dynamics of p90 Ribosomal S6 Kinase (RSK)

• Published in: The FASEB journal 2021-05, Vol.35 (S1), p.n/a, Article fasebj.2021.35.S1.04650
• Main Authors: Kobori, Evan, Taylor, Susan
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.2021.35.S1.04650

Protein kinase have evolved to be dynamic macromolecular switches that alternate between inactive and active conformations. Although most kinase are typically phosphorylated and activated by other kinases, relatively little is known about the detailed mechanistic steps required for one kinase to activate another. The p90 ribosomal S6 kinases (RSKs) lie downstream of the Ras‐MAPK pathway and regulates cell proliferation, cell survival, cell growth, and cell motility. RSK is an interesting model system to study kinase activation because it contains two distinct kinase domains, an N‐terminal kinase (NTK), and a C‐terminal kinase (CTK) in the same polypeptide chain. RSK has a complex activation mechanism that includes sequential phosphorylation events and requires two additional kinases: extracellular signal‐regulated kinase (ERK) and 3‐phosphoinositide‐dependent protein kinase 1 (PDK1). The precise structural details of RSK kinase activation are not fully understood and a more rigorous structural characterization could provide valuable insight into how kinase complexes assemble and how kinases activate other kinases. RSK activation begins with ERK binding to and activating the CTK. A major goal of this project is to determine the structure of the full length RSK‐ERK complex primarily utilizing cryoEM to gain insight into the orientations of three kinase domains relative to one another and to identify specific interaction networks that exist within the complex. We have determined a low resolution density map of the RSK‐ERK complex using negative stain EM and can identify each kinase domain.