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Structure paper

TitleStructural and mechanistic insights into the function of Leishmania ribosome lacking a single pseudouridine modification.
Journal, issue, pagesCell Rep, Vol. 43, Issue 5, Page 114203, Year 2024
Publish dateMay 28, 2024
AuthorsK Shanmugha Rajan / Saurav Aryal / Disha-Gajanan Hiregange / Anat Bashan / Hava Madmoni / Mika Olami / Tirza Doniger / Smadar Cohen-Chalamish / Pascal Pescher / Masato Taoka / Yuko Nobe / Aliza Fedorenko / Tanaya Bose / Ella Zimermann / Eric Prina / Noa Aharon-Hefetz / Yitzhak Pilpel / Toshiaki Isobe / Ron Unger / Gerald F Späth / Ada Yonath / Shulamit Michaeli /
PubMed AbstractLeishmania is the causative agent of cutaneous and visceral diseases affecting millions of individuals worldwide. Pseudouridine (Ψ), the most abundant modification on rRNA, changes during the ...Leishmania is the causative agent of cutaneous and visceral diseases affecting millions of individuals worldwide. Pseudouridine (Ψ), the most abundant modification on rRNA, changes during the parasite life cycle. Alterations in the level of a specific Ψ in helix 69 (H69) affected ribosome function. To decipher the molecular mechanism of this phenotype, we determine the structure of ribosomes lacking the single Ψ and its parental strain at ∼2.4-3 Å resolution using cryo-EM. Our findings demonstrate the significance of a single Ψ on H69 to its structure and the importance for its interactions with helix 44 and specific tRNAs. Our study suggests that rRNA modification affects translation of mRNAs carrying codon bias due to selective accommodation of tRNAs by the ribosome. Based on the high-resolution structures, we propose a mechanism explaining how the ribosome selects specific tRNAs.
External linksCell Rep / PubMed:38722744 / PubMed Central
MethodsEM (single particle)
Resolution2.4 - 2.97 Å
Structure data

15272

8a98

EMDB-15272, PDB-8a98:
CRYO-EM STRUCTURE OF LEISHMANIA MAJOR 80S RIBOSOME : snoRNA MUTANT
Method: EM (single particle) / Resolution: 2.46 Å

17216

8ovj

EMDB-17216, PDB-8ovj:
CRYO-EM STRUCTURE OF LEISHMANIA MAJOR 80S RIBOSOME : PARENTAL STRAIN
Method: EM (single particle) / Resolution: 2.4 Å

19576

8rxh

EMDB-19576, PDB-8rxh:
CRYO-EM STRUCTURE OF LEISHMANIA MAJOR 80S RIBOSOME WITH A/P/E-site tRNA AND mRNA : PARENTAL STRAIN
Method: EM (single particle) / Resolution: 2.93 Å

19582

8rxx

EMDB-19582, PDB-8rxx:
CRYO-EM STRUCTURE OF LEISHMANIA MAJOR 80S RIBOSOME WITH A/P/E-site tRNA AND mRNA : LM32Cs3H1 sKO STRAIN
Method: EM (single particle) / Resolution: 2.97 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-NA:
Unknown entry

ChemComp-K:
Unknown entry

ChemComp-HOH:
WATER

PDB-1h4f:
E. COLI BETA-KETOACYL [ACYL CARRIER PROTEIN] SYNTHASE I K328R

Source
  • leishmania major strain friedlin (eukaryote)
KeywordsRIBOSOME / CRYO-EM / LEISHMANIA MAJOR / 80S RIBOSOME snoRNA MUTANT / CRYO-EM LEISHMANIA MAJOR 80S RIBOSOME WILD TYPE / 80S

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