Related Experiment Video
Updated: Aug 8, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
Published on: March 9, 2012
A "Tug of War" Maintains a Dynamic Protein-Membrane Complex: Molecular Dynamics Simulations of C-Raf RBD-CRD Bound to
Zhen-Lu Li1, Priyanka Prakash2, Matthias Buck1,1,1,1,1
1Department of Physiology and Biophysics, Department of Neurosciences, Department of Pharmacology, Case Comprehensive Cancer Center and Center for Proteomics and Bioinformatics, Case Western Reserve University, School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
Abstract:
Association of Raf kinase with activated Ras triggers downstream signaling cascades toward regulating transcription in the cells' nucleus. Dysregulation of Ras-Raf signaling stimulates cancers. We investigate the C-Raf RBD and CRD regions when bound to oncogenic K-Ras4B at the membrane. All-atom molecular dynamics simulations suggest that the membrane plays an integral role in regulating the configurational ensemble of the complex. Remarkably, the complex samples a few states dynamically, reflecting a competition between C-Raf CRD- and K-Ras4B- membrane interactions. This competition arises because the interaction between the RBD and K-Ras is strong while the linker between the RBD and CRD is short. Such a mechanism maintains a modest binding for the overall complex at the membrane and is expected to facilitate fast signaling processes. Competition of protein-membrane contacts is likely a common mechanism for other multiprotein complexes, if not multidomain proteins at membranes.
Related Concept Videos
Membrane Fluidity
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is a relatively...
Protein Diffusion in the Membrane
Mechanisms of Membrane-bending
Membrane bending can happen due to intrinsic changes in lipid composition or extrinsic association with different proteins. The proteins involved...
Rab Proteins
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab Cascades
Small GTPases - Ras and Rho
Three regulatory proteins control their activity:

