PUBLICATION: Dimeric and Tetrameric Complexes of PICK1
Structure of Dimeric and Tetrameric Complexes of the BAR Domain Protein PICK1 Determined by Small-Angle X-Ray Scattering
Karlsen, M.L., Thorsen, T.S., Johner, N., Ammendrup-Johnsen, I., Erlendsson, S., Tian, X., Simonsen, J.B., Høiberg-Nielsen, R., Christensen, N.M., Khelashvili, G., Streicher, W., Teilum, K., Vestergaard, B., Weinstein, H., Gether, U., Arleth, L. and Madsen, K.L. Structure. 23(7):1258-70. doi:10.1016/j.str.2015.04.020 (2015)
PICK1 is a neuronal scaffolding protein containing a PDZ domain and an auto-inhibited BAR domain. BAR domains are membrane-sculpting protein modules generating membrane curvature and promoting membrane fission. Previous data suggest that BAR domains are organized in lattice-like arrangements when stabilizing membranes but little is known about structural organization of BAR domains in solution. Through a small-angle X-ray scattering (SAXS) analysis, we determine the structure of dimeric and tetrameric complexes of PICK1 in solution. SAXS and biochemical data reveal a strong propensity of PICK1 to form higher-order structures, and SAXS analysis suggests an offset, parallel mode of BAR-BAR oligomerization. Furthermore, unlike accessory domains in other BAR domain proteins, the positioning of the PDZ domains is flexible, enabling PICK1 to perform long-range, dynamic scaffolding of membrane-associated proteins. Together with functional data, these structural findings are compatible with a model in which oligomerization governs auto-inhibition of BAR domain function.