title: Organization and synergistic binding of copine I and annexin A1 on supported lipid bilayers observed by atomic force microscopy.
abstract: The transduction of signals across the plasma membrane of cells after receptor activation frequently involves the assembly of interacting protein molecules on the cytoplasmic face of the membrane. However, the structural organization and dynamics of the formation of such complexes has not been well defined. In this study atomic force microscopy was used to monitor the assemblies formed in vitro by two classes of calcium-dependent, membrane-binding proteins that participate in the formation of signaling complexes on membranes - the annexins and the copines. When applied to supported lipid bilayers composed of 25% brain phosphatidylserine and 75% dioleyl phosphatidylcholine in the presence of 1 mM Ca(2+) both human annexin A1 and human copine I bound only to specialized domains that appeared to be 0.5 to 1.0 nm lower than the rest of the bilayer. These domains may be enriched in phosphatidylserine and have a more disordered structure allowing probe penetration. Confinement of the binding of the proteins to these domains may be important in the process of concentrating other signaling proteins bound to the copine or annexin. The binding of the annexin promoted the growth of the domains and created additional binding space for the copine. This may reflect a general ability of annexins to alter membrane structure in such a way that C2 domain-containing proteins like copine can bind. Copine I formed a reticular lattice composed of linear elements approximately 45 nm long on the specialized domains. This lattice might provide a scaffold for the assembly and interaction of copine target proteins in signaling complexes.
authors.affiliation: Department of Pharmacology, University of Virginia, 1300 Jefferson Park Avenue, Charlottesvillle, VA 22908, USA. Creutz@virginia.edu
authors.forename: Carl E
authors.initials: CE
authors.lastname: Creutz
authors.forename: J Michael
authors.initials: JM
authors.lastname: Edwardson
mesh_terms: D017305:Annexin A1 / Q000737:chemistry* / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D018625:Microscopy, Atomic Force; D010718:Phosphatidylserines / Q000737:chemistry
chemical_list: D017305:Annexin A1; D002352:Carrier Proteins; D008051:Lipid Bilayers; D010718:Phosphatidylserines; C110203:copine