Unusual bipartite mode of interaction between the nonsense-mediated decay factors, UPF1 and UPF2.
EMBO J
; 28(15): 2293-306, 2009 Aug 05.
Article
em En
| MEDLINE
| ID: mdl-19556969
ABSTRACT
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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
RNA Mensageiro
/
Transativadores
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Estabilidade de RNA
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Mapeamento de Interação de Proteínas
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article