EMD-50259

Composite map
Single-particle
2.9 Å
EMD-50259 Deposition: 08/05/2024
Map released: 04/12/2024
Last modified: 18/12/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-50259

Yeast SDD1 Disome with Mbf1

EMD-50259

Composite map
Single-particle
2.9 Å
EMD-50259 Deposition: 08/05/2024
Map released: 04/12/2024
Last modified: 18/12/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Saccharomyces cerevisiae
Sample: glutaraldehyde crosslinked trisome fraction after sucrose density gradient centrifugation from yeast in vitro translation
Fitted models: 9f9s (Avg. Q-score: 0.54)

Deposition Authors: Denk T, Beckmann R
Multiprotein bridging factor 1 is required for robust activation of the integrated stress response on collided ribosomes.
PUBMED: 39566505
DOI: doi:10.1016/j.molcel.2024.10.029
ISSN: 1097-2765
ASTM: MOCEFL
Abstract:
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.