Figure 6
From: Galectin-1 dimers can scaffold Raf-effectors to increase H-ras nanoclustering
Comparison of current and our new model for the mechanism of action of Gal-1 as a nanocluster scaffold.
(A) Current model. Direct interaction of active H-ras and Gal-1 stabilizes nanocluster. H-ras (depicted as yellow oval) activation supposedly makes the C-terminal farnesyl chain of H-ras more accessible for the prenyl-binding pocket of Gal-1 (depicted as a blue hexagon). This mechanistic step has not been described for other, similar trafficking chaperones, such as GDIs or PDEδ. Instead the spontaneous, activation state independent dissociation from the membrane is the basis for complexation by such chaperones in the cytoplasm74,75. (B) In the new model proposed here, Raf effectors (depicted as violet rectangles) are recruited to active H-ras in nanoclusters on the plasma membrane. At higher concentrations Gal-1 can dimerize. Gal-1 binds directly to the Ras binding domain (RBD) of effectors, such as Raf. Thus, dimeric Gal-1 could stabilize effector (Raf)-dimers, which then act as the actual ‘scaffold’ for H-ras nanocluster. Note that effector and Gal-1 can form complexes already in the cytoplasm. Stacked dimers of H-ras + effector (Raf) + Gal-1 (box to right) would be nucleating the growth of H-ras nanocluster, a process that may be supported by the membrane environment.
