Geometric Curvature Sensing of Alpha-Helical Proteins

Abstract

Understanding how specific proteins are recruited to membranes is crucial to understanding key biological functions. Membrane curvature sensing is increasingly recognized as a powerful means for guiding protein localization, coupling protein binding to the local membrane geometry. The mechanisms underlying curvature sensing remain poorly quantified, however. We focus on the two curvature-associated proteins that share an amphipathic alpha-helical structure. The first, SpoVM, is a small (26 residue) protein from Bacillus subtillus that has recently been shown to preferentially bind to convex surfaces [K.S. Ramamurthy et al., Science 323: 1354 (2009)]. The second is the 23 amino acid N-terminal helical domain of Sar1, which initiates the assembly of COPII coated vesicles at the endoplasmic reticulum and which recent work [Parthasarthy Lab, unpublished] has shown to dramatically alter membrane rigidity. Using both microfabricated surfaces that present controlled curvatures to the proteins and optical-trap based assays involving dynamic membrane deformation, we quantify the curvature dependence of the membrane binding affinity of these structurally similar yet functionally disparate proteins.