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Structure paper

TitleZNF598 Is a Quality Control Sensor of Collided Ribosomes.
Journal, issue, pagesMol Cell, Vol. 72, Issue 3, Page 469-481.e7, Year 2018
Publish dateNov 1, 2018
AuthorsSzymon Juszkiewicz / Viswanathan Chandrasekaran / Zhewang Lin / Sebastian Kraatz / V Ramakrishnan / Ramanujan S Hegde /
PubMed AbstractAberrantly slow translation elicits quality control pathways initiated by the ubiquitin ligase ZNF598. How ZNF598 discriminates physiologic from pathologic translation complexes and ubiquitinates ...Aberrantly slow translation elicits quality control pathways initiated by the ubiquitin ligase ZNF598. How ZNF598 discriminates physiologic from pathologic translation complexes and ubiquitinates stalled ribosomes selectively is unclear. Here, we find that the minimal unit engaged by ZNF598 is the collided di-ribosome, a molecular species that arises when a trailing ribosome encounters a slower leading ribosome. The collided di-ribosome structure reveals an extensive 40S-40S interface in which the ubiquitination targets of ZNF598 reside. The paucity of 60S interactions allows for different ribosome rotation states, explaining why ZNF598 recognition is indifferent to how the leading ribosome has stalled. The use of ribosome collisions as a proxy for stalling allows the degree of tolerable slowdown to be tuned by the initiation rate on that mRNA; hence, the threshold for triggering quality control is substrate specific. These findings illustrate how higher-order ribosome architecture can be exploited by cellular factors to monitor translation status.
External linksMol Cell / PubMed:30293783 / PubMed Central
MethodsEM (single particle)
Resolution3.8 - 6.8 Å
Structure data

0192

6hcf

EMDB-0192, PDB-6hcf:
Structure of the rabbit 80S ribosome stalled on globin mRNA at the stop codon
Method: EM (single particle) / Resolution: 3.9 Å

0194

6hcj

EMDB-0194, PDB-6hcj:
Structure of the rabbit 80S ribosome on globin mRNA in the rotated state with A/P and P/E tRNAs
Method: EM (single particle) / Resolution: 3.8 Å

0195

6hcm

EMDB-0195: Multi-body refined map of the rabbit 80S stalled on globin mRNA at the stop codon
PDB-6hcm: Structure of the rabbit collided di-ribosome (stalled monosome)
Method: EM (single particle) / Resolution: 6.8 Å

0197

6hcq

EMDB-0197: Multi-body refined map of the rabbit 80S collided with a stalled 80S
PDB-6hcq: Structure of the rabbit collided di-ribosome (collided monosome)
Method: EM (single particle) / Resolution: 6.5 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-SF4:
IRON/SULFUR CLUSTER

ChemComp-HOH:
WATER

Source
  • oryctolagus cuniculus (rabbit)
  • homo sapiens (human)
  • Rabbit (rabbit)
KeywordsRIBOSOME / Translation / Quality Control

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