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TitleStructure of the mammalian ribosome as it decodes the selenocysteine UGA codon.
Journal, issue, pagesScience, Vol. 376, Issue 6599, Page 1338-1343, Year 2022
Publish dateJun 17, 2022
AuthorsTarek Hilal / Benjamin Y Killam / Milica Grozdanović / Malgorzata Dobosz-Bartoszek / Justus Loerke / Jörg Bürger / Thorsten Mielke / Paul R Copeland / Miljan Simonović / Christian M T Spahn /
PubMed AbstractThe elongation of eukaryotic selenoproteins relies on a poorly understood process of interpreting in-frame UGA stop codons as selenocysteine (Sec). We used cryo-electron microscopy to visualize Sec ...The elongation of eukaryotic selenoproteins relies on a poorly understood process of interpreting in-frame UGA stop codons as selenocysteine (Sec). We used cryo-electron microscopy to visualize Sec UGA recoding in mammals. A complex between the noncoding Sec-insertion sequence (SECIS), SECIS-binding protein 2 (SBP2), and 40 ribosomal subunit enables Sec-specific elongation factor eEFSec to deliver Sec. eEFSec and SBP2 do not interact directly but rather deploy their carboxyl-terminal domains to engage with the opposite ends of the SECIS. By using its Lys-rich and carboxyl-terminal segments, the ribosomal protein eS31 simultaneously interacts with Sec-specific transfer RNA (tRNA) and SBP2, which further stabilizes the assembly. eEFSec is indiscriminate toward l-serine and facilitates its misincorporation at Sec UGA codons. Our results support a fundamentally distinct mechanism of Sec UGA recoding in eukaryotes from that in bacteria.
External linksScience / PubMed:35709277 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 3.1 Å
Structure data

EMDB-14751, PDB-7zjw:
Rabbit 80S ribosome as it decodes the Sec-UGA codon
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-14752, PDB-7zjx:
Rabbit 80S ribosome programmed with SECIS and SBP2
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM / Guanosine triphosphate

ChemComp-SER:
SERINE / Serine

ChemComp-MG:
Unknown entry

ChemComp-K:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-NA:
Unknown entry

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
  • cricket paralysis virus
  • rattus norvegicus (Norway rat)
  • oryctolagus cuniculus (rabbit)
KeywordsRIBOSOME / Selenocysteine / recoding / 80S

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