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Clerici, M.* ; Mourao, A. ; Gutsche, I.* ; Gehring, N.H.* ; Hentze, M.W.* ; Kulozik, A.* ; Kadlec, J.* ; Sattler, M. ; Cusack, S.*

Unusual bipartite mode of interaction between the nonsense-mediated decay factors, UPF1 and UPF2.

EMBO J. 28, 2293-2306 (2009)
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Nonsense-mediated decay (NMD) is a eukaryotic quality control mechanism that degrades mRNAs carrying premature stop codons. In mammalian cells, NMD is triggered when UPF2 bound to UPF3 on a downstream exon junction complex interacts with UPF1 bound to a stalled ribosome. We report structural studies on the interaction between the C-terminal region of UPF2 and intact UPF1. Crystal structures, confirmed by EM and SAXS, show that the UPF1 CH-domain is docked onto its helicase domain in a fixed configuration. The C-terminal region of UPF2 is natively unfolded but binds through separated alpha-helical and beta-hairpin elements to the UPF1 CH-domain. The alpha-helical region binds sixfold more weakly than the beta-hairpin, whereas the combined elements bind 80-fold more tightly. Cellular assays show that NMD is severely affected by mutations disrupting the beta-hairpin binding, but not by those only affecting alpha-helix binding. We propose that the bipartite mode of UPF2 binding to UPF1 brings the ribosome and the EJC in close proximity by forming a tight complex after an initial weak encounter with either element.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter mRNA quality control; nonsense mediate decay (NMD); NMR; UPF1; UPF2; X-ay crystallography; messenger-rna decay; exon-junction complex; quality-control; surveillance complex; unstructured proteins; termination codon; mammalian-cells; nmd factors; pathway; translation
ISSN (print) / ISBN 0261-4189
e-ISSN 1460-2075
Zeitschrift EMBO Journal, The
Quellenangaben Band: 28, Heft: 15, Seiten: 2293-2306 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Heidelberg, Germany
Begutachtungsstatus Peer reviewed