English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Structure of substrate-bound SMG1-8-9 kinase complex reveals molecular basis for phosphorylation specificity

MPS-Authors
/persons/resource/persons244420

Langer,  Lukas M.
Conti, Elena / Structural Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons245076

Gat,  Yair
Conti, Elena / Structural Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons77784

Bonneau,  Fabien
Conti, Elena / Structural Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons77867

Conti,  Elena
Conti, Elena / Structural Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society;

External Resource
No external resources are shared
Fulltext (public)

elife-57127-v2.pdf
(Any fulltext), 4MB

Supplementary Material (public)
There is no public supplementary material available
Citation

Langer, L. M., Gat, Y., Bonneau, F., & Conti, E. (2020). Structure of substrate-bound SMG1-8-9 kinase complex reveals molecular basis for phosphorylation specificity. ELIFE, 9: e57127. doi:10.7554/eLife.57127.


Cite as: http://hdl.handle.net/21.11116/0000-0006-C9D2-A
Abstract
PI3K-related kinases (PIKKs) are large Serine/Threonine (Ser/Thr)-protein kinases central to the regulation of many fundamental cellular processes. PIKK family member SMG1 orchestrates progression of an RNA quality control pathway, termed nonsense-mediated mRNA decay (NMD), by phosphorylating the NMD factor UPF1. Phosphorylation of UPF1 occurs in its unstructured N- and C-terminal regions at Serine/Threonine-Glutamine (SQ) motifs. How SMG1 and other PIKKs specifically recognize SQ motifs has remained unclear. Here, we present a cryo-electron microscopy (cryo-EM) reconstruction of a human SMG1-8-9 kinase complex bound to a UPF1 phosphorylation site at an overall resolution of 2.9 angstrom. This structure provides the first snapshot of a human PIKK with a substrate-bound active site. Together with biochemical assays, it rationalizes how SMG1 and perhaps other PIKKs specifically phosphorylate Ser/Thr-containing motifs with a glutamine residue at position +1 and a hydrophobic residue at position -1, thus elucidating the molecular basis for phosphorylation site recognition.