title: Protein interactions and membrane geometry.
abstract: The difficulty in growing crystals for x-ray diffraction analysis has hindered the determination of membrane protein structures. However, this is changing with the advent of a new method for growing high quality membrane protein crystals from the lipidic cubic phase. Although successful, the mechanism underlying this method has remained unclear. Here, we present a theoretical analysis of the process. We show that it is energetically favorable for proteins embedded in the highly curved cubic phase to cluster together in flattened regions of the membrane. This stabilizes the lamellar phase, permitting its outgrowth from the cubic phase. A kinetic barrier-crossing model is developed to determine the free energy barrier to crystallization from the time-dependent growth of protein clusters. Determining the values of key parameters provides both a rational basis for optimizing the experimental procedure for membrane proteins that have not yet been crystallized and insight into the analogous cubic to lamellar transitions in cells. We also discuss the implications of this mechanism for protein sorting at the exit sites of the Golgi and endoplasmic reticulum and the general stabilization of membrane structures.
authors.affiliation: Department of Physics, University of California, Berkeley, California 94720, USA. mgrabe@itsa.ucsf.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Grabe
authors.forename: John
authors.initials: J
authors.lastname: Neu
authors.forename: George
authors.initials: G
authors.lastname: Oster
authors.forename: Peter
authors.initials: P
authors.lastname: Nollert
mesh_terms: D003198:Computer Simulation; D003460:Crystallization / Q000379:methods*; D004548:Elasticity; D004735:Energy Transfer; D008051:Lipid Bilayers / Q000737:chemistry*; D046911:Macromolecular Substances; D008560:Membrane Fluidity; D008565:Membrane Proteins / Q000138:chemical synthesis / Q000737:chemistry*; D008567:Membranes, Artificial; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D009038:Motion; D011487:Protein Conformation; D055672:Static Electricity; D013314:Stress, Mechanical; D013499:Surface Properties
chemical_list: D008051:Lipid Bilayers; D046911:Macromolecular Substances; D008565:Membrane Proteins; D008567:Membranes, Artificial