Structural Biochemistry/Membrane Proteins/Membrane Curvature

Introduction

 * Curved membranes recruit large densities of alkylated proteins independent of affinity, with no requirement for specific recognition motifs. The biological curved membrane is identified the lipid composition and the action of membrane-bending proteins.

Function

 * The membrane curvature can regulate the localization of proteins with specific recognition motifs. Amphipathic alpha helices are critical membrane curvature sensors with a large range of proteins included with larger affinity for positively curved membranes through the recognition of curve defects in lipid packing. The membrane curvature dependent measurements, mostly made in vitro, are averaged across liposomes of variant diameter. These measurements reduce the accuracy and make calculation of affinity more difficult.

Hypothesis

 * Scientist Dimitrios Stamou and his fellows eliminated the problem of the calculations by using the fluorescence microscopy to determine membrane curvature- selective binding on individual liposomes. Their studies reveal the curved membranes can accommodate at a high density of amphiphilic molecules. Therefore, the sensing of membrane curvature emerges consists the property of lipid membranes without any specific proteins anchored by hydrophobic motif.


 * The single liposome binding measurements used biotinylated liposomes of varied sizes, which then labeled with a chromosphore and immobilized by streptavidin. The fluorescence intensity was used to measure the individual liposomal diameters. Another chromophore was used to tag the molecule of interest, and the ratio of the two fluorescent signals in order to find the density of labeled molecules to each individual liposome.


 * The binding of amphipathic alpha-helical peptides to the immobilized liposomes were discovered to plot against the amphipathic alpha-helical diameter. The density of peptide stayed constant for measurements of 200nm and above; the measurement increases sharply below 50nm. The equilibrium constant Kd was discovered with little contribution to curvature-selective binding at concentration below Kd.

Prove

 * A geometrical model in highly-curved membranes with a greater density of lipid packing defects provide sites for amphiphilic molecules to insert themselves. The density of binding increases the area of outer leaflet of a membrane. At higher concentration, the interactions are saturated and the defect density effect will predominate. After all, the peptide density will become proportional to defect density, the results for prptides will then fit with the model.


 * The model can determine the insertion of any amphiphilic molecules with curvature selective. Scientist uses simple alkyl chains with palmitoyl motif to test the property of model. All alkyl chains are sensors of membrane curvature comparable to amphipathic alpha-helical peptides. The head group of alkyl chains without any influence alter to chain itself. Also, the proteins can be added to the chains without affect the curvature-sensing properties.

Conclusion

 * Overall, the membrane curvature is a generic mechanism to influence the localization of all amphiphilic molecules. Under the effect of concentration of fusogenic lipids in the membrane, membrane curvature can play an important role for protein trafficking and cell signaling in the study of science.

Reference

 * Hatzakis, N. S., Bhatia, V. K., Larsen, J., Madsen, K. L., Bolinger, P-Y., Kunding, A. H., Castillo, J., Gether, U., Hedegård, P. & Stamou, D. How curved membranes recruit amphipathic helices and protein anchoring motifs. Nature Chemical Biology (13 September 2009). doi:10.1038/nchembio.213