title: Conformational transitions in human translin enable nucleic acid binding.
abstract: Translin is a highly conserved RNA- and DNA-binding protein that plays essential roles in eukaryotic cells. Human translin functions as an octamer, but in the octameric crystallographic structure, the residues responsible for nucleic acid binding are not accessible. Moreover, electron microscopy data reveal very different octameric configurations. Consequently, the functional assembly and the mechanism of nucleic acid binding by the protein remain unclear. Here, we present an integrative study combining small-angle X-ray scattering (SAXS), site-directed mutagenesis, biochemical analysis and computational techniques to address these questions. Our data indicate a significant conformational heterogeneity for translin in solution, formed by a lesser-populated compact octameric state resembling the previously solved X-ray structure, and a highly populated open octameric state that had not been previously identified. On the other hand, our SAXS data and computational analyses of translin in complex with the RNA oligonucleotide (GU)12 show that the internal cavity found in the octameric assemblies can accommodate different nucleic acid conformations. According to this model, the nucleic acid binding residues become accessible for binding, which facilitates the entrance of the nucleic acids into the cavity. Our data thus provide a structural basis for the functions that translin performs in RNA metabolism and transport.
authors: Joint BSC-IRB research programme in Computational Biology, Barcelona Supercomputing Center (BSC), Jordi Girona 29, Barcelona 08034, Spain, Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel, Blavatnik School of Computer Science, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel, Bioinformatics Knowledge Unit, The Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel and Centre de Biochimie Structurale, INSERM U1054, CNRS UMR 5048, Université Montpellier 1 and 2, F-34090 Montpellier, France.
authors: Laura
authors: L
authors: Pérez-Cano
authors: Elad
authors: E
authors: Eliahoo
authors: Keren
authors: K
authors: Lasker
authors: Haim J
authors: HJ
authors: Wolfson
authors: Fabian
authors: F
authors: Glaser
authors: Haim
authors: H
authors: Manor
authors: Pau
authors: P
authors: Bernadó
authors: Juan
authors: J
authors: Fernández-Recio
mesh_terms: D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D055503:Protein Multimerization; D012313:RNA / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C095563:TSN protein, human; D012313:RNA
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