title: Molecular Architecture of Full-length TRF1 Favors Its Interaction with DNA.
abstract: Telomeres are specific DNA-protein structures found at both ends of eukaryotic chromosomes that protect the genome from degradation and from being recognized as double-stranded breaks. In vertebrates, telomeres are composed of tandem repeats of the TTAGGG sequence that are bound by a six-subunit complex called shelterin. Molecular mechanisms of telomere functions remain unknown in large part due to lack of structural data on shelterins, shelterin complex, and its interaction with the telomeric DNA repeats. TRF1 is one of the best studied shelterin components; however, the molecular architecture of the full-length protein remains unknown. We have used single-particle electron microscopy to elucidate the structure of TRF1 and its interaction with telomeric DNA sequence. Our results demonstrate that full-length TRF1 presents a molecular architecture that assists its interaction with telometic DNA and at the same time makes TRFH domains accessible to other TRF1 binding partners. Furthermore, our studies suggest hypothetical models on how other proteins as TIN2 and tankyrase contribute to regulate TRF1 function.
authors: From the Structural Biology and Biocomputing Programme, Electron Microscopy Unit, jboskovic@cnio.es.
authors: Jasminka
authors: J
authors: Boskovic
authors: Structural Biology and Biocomputing Programme, Crystallography and Protein Engineering Unit, and.
authors: Jaime
authors: J
authors: Martinez-Gago
authors: Molecular Oncology Programme, Telomeres and Telomerase Group, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
authors: Marinela
authors: M
authors: Mendez-Pertuz
authors: From the Structural Biology and Biocomputing Programme, Electron Microscopy Unit.
authors: Alberto
authors: A
authors: Buscato
authors: Structural Biology and Biocomputing Programme, Crystallography and Protein Engineering Unit, and.
authors: Jorge Luis
authors: JL
authors: Martinez-Torrecuadrada
authors: Molecular Oncology Programme, Telomeres and Telomerase Group, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain mblasco@cnio.es.
authors: Maria A
authors: MA
authors: Blasco
mesh_terms: D000818:Animals; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D000072417:Protein Domains; D061987:Sf9 Cells; D018411:Spodoptera; D020080:Tandem Repeat Sequences; D038501:Tankyrases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000737:chemistry* / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D035321:Telomeric Repeat Binding Protein 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: C534796:TRF2 protein, mouse; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; C499083:Tinf2 protein, mouse; D004247:DNA; D038501:Tankyrases; C498822:Tnks protein, mouse
keywords: DNA binding protein; electron microscopy (EM); protein structure; shelterin; telomere; telomeric repeat binding factor1 (TRF1); telomeric repeat-binding factor 1 (TERF1)