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TitleMultiprotein bridging factor 1 is required for robust activation of the integrated stress response on collided ribosomes.
Journal, issue, pagesMol Cell, Vol. 84, Issue 23, Page 4594-44611.e9, Year 2024
Publish dateDec 5, 2024
AuthorsKyusik Q Kim / Jeffrey J Li / Ankanahalli N Nanjaraj Urs / Miguel E Pacheco / Victor Lasehinde / Timo Denk / Petr Tesina / Shota Tomomatsu / Yoshitaka Matsuo / Elesa McDonald / Roland Beckmann / Toshifumi Inada / Rachel Green / Hani S Zaher /
PubMed AbstractIn yeast, multiprotein bridging factor 1 (Mbf1) has been proposed to function in the integrated stress response (ISR) as a transcriptional coactivator by mediating a direct interaction between ...In yeast, multiprotein bridging factor 1 (Mbf1) has been proposed to function in the integrated stress response (ISR) as a transcriptional coactivator by mediating a direct interaction between general transcription machinery and the process's key effector, Gcn4. However, mounting evidence has demonstrated that Mbf1 (and its human homolog EDF1) is recruited to collided ribosomes, a known activator of the ISR. In this study, we connect these otherwise seemingly disparate functions of Mbf1. Our biochemical and structural analyses reveal that Mbf1 functions as a core ISR factor by interacting with collided ribosomes to mediate Gcn2 activation. We further show that Mbf1 serves no role as a transcriptional coactivator of Gcn4. Instead, Mbf1 is required for optimal stress-induced eukaryotic initiation factor 2α (eIF2α) phosphorylation and downstream de-repression of GCN4 translation. Collectively, our data establish that Mbf1 functions in ISR signaling by acting as a direct sensor of stress-induced ribosome collisions.
External linksMol Cell / PubMed:39566505 / PubMed Central
MethodsEM (single particle)
Resolution2.66 - 2.92 Å
Structure data

EMDB-50170: Stalled ribosome with Mbf1 N-terminus
Method: EM (single particle) / Resolution: 2.92 Å

EMDB-50171: Collided ribosome with Mbf1 C-terminus
Method: EM (single particle) / Resolution: 2.66 Å

50259

9f9s

EMDB-50259, PDB-9f9s:
Yeast SDD1 Disome with Mbf1
Method: EM (single particle) / Resolution: 2.9 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-K:
Unknown entry

ChemComp-SPD:
SPERMIDINE

Source
  • saccharomyces cerevisiae (brewer's yeast)
KeywordsRIBOSOME / quality control / frame shifting / collision

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