English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/111185
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Structure of the dimeric exonuclease TREX1 in complex with DNA displays a proline-rich binding site for WW domains

AutorBrucet, Marina; Querol-Audí, Jordi ; Serra, Maria; Ramírez-Espain, Ximena; Bertlik, Kamila; Ruiz, Lidia; Lloberas, Jorge; Macías, María J.; Fita, Ignacio ; Celada, Antonio
Fecha de publicación11-may-2007
EditorAmerican Society for Biochemistry and Molecular Biology
CitaciónJournal of Biological Chemistry 282(19): 14547-14557 (2007)
ResumenTREX1 is the most abundant mammalian 3′ → 5′ DNA exonuclease. It has been described to form part of the SET complex and is responsible for the Aicardi-Goutières syndrome in humans. Here we show that the exonuclease activity is correlated to the binding preferences toward certain DNA sequences. In particular, we have found three motifs that are selected, GAG, ACA, and CTGC. To elucidate how the discrimination occurs, we determined the crystal structures of two murine TREX1 complexes, with a nucleotide product of the exonuclease reaction, and with a single-stranded DNA substrate. Using confocal microscopy, we observed TREX1 both in nuclear and cytoplasmic subcellular compartments. Remarkably, the presence of TREX1 in the nucleus requires the loss of a C-terminal segment, which we named leucine-rich repeat 3. Furthermore, we detected the presence of a conserved proline-rich region on the surface of TREX1. This observation points to interactions with proline-binding domains. The potential interacting motif >PPPVPRPP> does not contain aromatic residues and thus resembles other sequences that select SH3 and/or Group 2WW domains. By means of nuclear magnetic resonance titration experiments, we show that, indeed, a polyproline peptide derived from the murine TREX1 sequence interacted with the WW2 domain of the elongation transcription factor CA150. Coimmunoprecipitation studies confirmed this interaction with the full-length TREX1 protein, thereby suggesting that TREX1 participates in more functional complexes than previously thought. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.
Versión del editorhttp://dx.doi.org/10.1074/jbc.M700236200
Identificadoresdoi: 10.1074/jbc.M700236200
issn: 0021-9258
Aparece en las colecciones: (IBMB) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
accesoRestringido.pdf15,38 kBAdobe PDFVista previa
Mostrar el registro completo

Artículos relacionados:

NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.