Bacterial ribosome collision sensing by a MutS DNA repair ATPase paralogue.

Ribosome stalling during translation is detrimental to cellular fitness, but how this is sensed and elicits recycling of ribosomal subunits and quality control of associated mRNA and incomplete nascent chains is poorly understood. Here we uncover Bacillus subtilis MutS2, a member of the conserved MutS family of ATPases that function in DNA mismatch repair, as an unexpected ribosome-binding protein with an essential function in translational quality control. Cryo-electron microscopy analysis of affinity-purified native complexes shows that MutS2 functions in sensing collisions between stalled and translating ribosomes and suggests how ribosome collisions can serve as platforms to deploy downstream processes: MutS2 has an RNA endonuclease small MutS-related (SMR) domain, as well as an ATPase/clamp domain that is properly positioned to promote ribosomal subunit dissociation, which is a requirement both for ribosome recycling and for initiation of ribosome-associated protein quality control (RQC).

Mechanisms of Cotranslational Protein Maturation in Bacteria.

Growing cells invest a significant part of their biosynthetic capacity into the production of proteins. To become functional, newly-synthesized proteins must be N-terminally processed, folded and often translocated to other cellular compartments. A general strategy is to integrate these protein maturation processes with translation, by cotranslationally engaging processing enzymes, chaperones and targeting factors with the nascent polypeptide.

Interactions between nascent proteins translated by adjacent ribosomes drive homomer assembly.

Accurate assembly of newly synthesized proteins into functional oligomers is crucial for cell activity. In this study, we investigated whether direct interaction of two nascent proteins, emerging from nearby ribosomes (co-co assembly), constitutes a general mechanism for oligomer formation. We used proteome-wide screening to detect nascent chain-connected ribosome pairs and identified hundreds of homomer subunits that co-co assemble in human cells.

Cellular Consequences of Diminished Protein O-Mannosyltransferase Activity in Baker's Yeast.

-Mannosylation is a type of protein glycosylation initiated in the endoplasmic reticulum (ER) by the protein -mannosyltransferase (PMT) family. Despite the vital role of -mannosylation, its molecular functions and regulation are not fully characterized. To further explore the cellular impact of protein -mannosylation, we performed a genome-wide screen to identify mutants with increased sensitivity towards the PMT-specific inhibitor compound R3A-5a.