2WJY

Crystal structure of the complex between human nonsense mediated decay factors UPF1 and UPF2 Orthorhombic form

Summary for 2WJY

• Entry DOI: 10.2210/pdb2wjy/pdb
• Related: 2IYK 2WJV
• Descriptor: REGULATOR OF NONSENSE TRANSCRIPTS 1, ZINC ION, SULFATE ION, ... (4 entities in total)
• Functional Keywords: nonsense mediated decay, zinc-finger, atp-binding, metal-binding, upf2, upf1, helicase, hydrolase, nonsense-mediated mrna decay, phosphoprotein, nucleotide-binding
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: Q92900
• Total number of polymer chains: 1
• Total formula weight: 90948.97

Authors

Clerici, M.,Mourao, A.,Gutsche, I.,Gehring, N.H.,Hentze, M.W.,Kulozik, A.,Kadlec, J.,Sattler, M.,Cusack, S. (deposition date: 2009-06-01, release date: 2009-07-07, Last modification date: 2023-12-13)

Primary citation

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-, 2009

PubMed 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.

PubMed: 19556969
DOI: 10.1038/EMBOJ.2009.175

Experimental method

X-RAY DIFFRACTION (2.5 Å)