TY  - JOUR
AU  - Wruck, Florian
AU  - Schmitt, Jaro
AU  - Till, Katharina
AU  - Fenzl, Kai
AU  - Bertolini, Matilde
AU  - Tippmann, Frank
AU  - Katranidis, Alexandros
AU  - Bukau, Bernd
AU  - Kramer, Günter
AU  - Tans, Sander J
TI  - Co-translational ribosome pairing enables native assembly of misfolding-prone subunits.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-01713
SP  - 7626
PY  - 2025
N1  - A250 30.09.2023 geschlossen
AB  - Protein complexes are pivotal to most cellular processes. Emerging evidence indicating dimer assembly by pairs of ribosomes suggests yet unknown folding mechanisms involving two nascent chains. Here, we show that co-translational ribosome pairing allows their nascent chains to 'chaperone each other', thus enabling the formation of coiled-coil homodimers from subunits that misfold individually. We developed an integrated single-molecule fluorescence and force spectroscopy approach to probe the folding and assembly of two nascent chains extending from nearby ribosomes, using the intermediate filament lamin as a model system. Ribosome proximity during early translation stages is found to be critical: when interactions between nascent chains are inhibited or delayed, they become trapped in stable misfolded states that are no longer assembly-competent. Conversely, early interactions allow the two nascent chains to nucleate native-like quaternary structures that grow in size and stability as translation advances. We conjecture that protein folding mechanisms enabled by ribosome cooperation are more broadly relevant to intermediate filaments and other protein classes.
LB  - PUB:(DE-HGF)16
C6  - pmid:40817089
C2  - pmc:PMC12356879
DO  - DOI:10.1038/s41467-025-61500-y
UR  - https://inrepo02.dkfz.de/record/303649
ER  -