Rapidly Accelerated Fibrosarcoma (RAF) Kinase is central to the MAPK Signaling Cascade. The three isoforms of RAF (A/B/C) contain 3 conserved domains. The interplays among those domains have not been investigated directly. X-ray crystallography, cryo-EM, and NMR have been successfully employed to determine the truncated domains of RAF. These reported structures lack environmental context that is necessary to detail physiologically relevant components of regulation such as protein-protein interactions (PPI) and insight regarding isoform-specific mechanisms. Conserved mechanisms of RAF regulation highlight dimerization and membrane localization by RAS-GTP. According to the accepted model, inactive RAF kinase is monomeric, autoinhibited, and cytosolic while activated RAF is membrane recruited and dimerized; however—direct evidence and key details are still missing.  The current model lacks how spatial regulation is able to activate RAF at the plasma membrane. Using a chemical biology approach to target this complex biological system (MAPK Pathway), we seek to exert spatial control of RAF to explore the effects of membrane localization on RAF activity and to uncover physiologically relevant regulatory mechanisms. Our strategy employs biochemical approaches to elucidate membrane associated mechanisms of RAF kinase regulation. By spatially reorganizing BRAF and CRAF, we seek to recapitulate physiologically relevant PPI to reveal distinct isoform-dependent mechanisms of regulation.<br/>

Investigation of membrane-associated mechanisms of RAF kinase

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.