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SUMMARY:Molecular insights into Raf activation: Significance of Membrane Bi
 nding Kinetics and its Modulation by Local Membrane Environments
LOCATION:Chemistry A101
TZID:America/Denver
DTSTART:20241121T160000
UID:2026-04-28-18-32-44@natsci.colostate.edu
DTSTAMP:20260428T183244
Description:About the Seminar:\n\nRaf is an important kinase that initiates
  the three-tiered Raf-MEK-ERK signaling cascade in response to diverse rec
 eptor stimuli. Understanding the regulation of Raf membrane binding is cru
 cial to fully grasp its activation mechanisms\, as Raf activation exclusiv
 ely occurs on membrane surfaces. However\, there is a notable lack of quan
 titative experimental studies exploring how Raf integrates both protein an
 d lipid inputs for proper activation and deactivation. To address this gap
 \, we used single-molecule total internal reflection fluorescence microsco
 py (smTIRF) and fluorescence correlation spectroscopy (FCS) to examine the
  molecular binding and diffusion of Raf on supported lipid membranes. Our 
 findings reveal functional coupling between the Ras binding domain (RBD) a
 nd the cysteine-rich domain (CRD) within Raf’s regulatory region. This c
 oupling gives rise to distinct modulation of the membrane association and 
 dissociation rates of Raf\, demonstrating a strong dependency of membrane 
 binding kinetics on the surface density of Ras and anionic lipids. Additio
 nally\, we investigated how Ras-Raf complex formation and membrane environ
 ments resist deactivation by GTPase-activating proteins (GAPs). Our result
 s provide new insights into the kinetic mechanisms underlying Raf activati
 on\, particularly the release of its autoinhibited complex and the transit
 ion from monomer to dimer in the context of Ras nanoclusters.\n\n&nbsp\;\n
 \nAbout the Speaker:\n\nDr. Lee is an Assistant Professor in the Departmen
 t of Chemistry and Biochemistry at San Diego State University. He earned h
 is Bachelor\\'s and Master\\'s degrees in Chemistry from Kookmin Universit
 y\, followed by a Ph.D. in Chemistry from Seoul National University. After
  completing his doctoral studies\, he conducted postdoctoral research at U
 C Berkeley before joining the faculty at SDSU in 2018. Dr. Lee is a recipi
 ent of the NSF CAREER award\, and his research focuses on understanding th
 e molecular mechanisms of signal transduction using optical microscopy and
  spectroscopy techniques.\n\n&nbsp\; 4:00 pm
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