title: Automated determination of fibrillar structures by simultaneous model building and fiber diffraction refinement.
abstract: For highly oriented fibrillar molecules, three-dimensional structures can often be determined from X-ray fiber diffraction data. However, because of limited information content, structure determination and validation can be challenging. We demonstrate that automated structure determination of protein fibers can be achieved by guiding the building of macromolecular models with fiber diffraction data. We illustrate the power of our approach by determining the structures of six bacteriophage viruses de novo using fiber diffraction data alone and together with solid-state NMR data. Furthermore, we demonstrate the feasibility of molecular replacement from monomeric and fibrillar templates by solving the structure of a plant virus using homology modeling and protein-protein docking. The generated models explain the experimental data to the same degree as deposited reference structures but with improved structural quality. We also developed a cross-validation method for model selection. The results highlight the power of fiber diffraction data as structural constraints.
authors.affiliation: Department of Biochemistry and Structural Biology, Lund University, Lund, Sweden.
authors.forename: Wojciech
authors.identifier: 0000000277896779
authors.initials: W
authors.lastname: Potrzebowski
authors.affiliation: Department of Biochemistry and Structural Biology, Lund University, Lund, Sweden.
authors.forename: Ingemar
authors.initials: I
authors.lastname: André
mesh_terms: D057205:Automation, Laboratory / Q000379:methods*; D017912:Inovirus / Q000648:ultrastructure; D008958:Models, Molecular; D011506:Proteins / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods*
chemical_list: D011506:Proteins