7ZQ6

70S E. coli ribosome with truncated uL23 and uL24 loops and a stalled filamin domain 5 nascent chain

7ZQ6 の概要

• エントリーDOI: 10.2210/pdb7zq6/pdb
• EMDBエントリー: 14865
• 分子名称: 50S ribosomal protein L28, 23S rRNA, 50S ribosomal protein L2, ... (32 entities in total)
• 機能のキーワード: ribosome, exit tunnel, structural modification, ribosomal protein, folded nascent chain
• 由来する生物種: Dictyostelium discoideum; 詳細
• タンパク質・核酸の鎖数: 32
• 化学式量合計: 1368735.09

構造登録者

Mitropoulou, A.,Wlodarski, T.,Ahn, M.,Becker, T.A.,Beckmann, R.,Cabrita, L.D.,Christodoulou, J. (登録日: 2022-04-29, 公開日: 2022-08-10, 最終更新日: 2024-10-09)

主引用文献

Ahn, M.,Wlodarski, T.,Mitropoulou, A.,Chan, S.H.S.,Sidhu, H.,Plessa, E.,Becker, T.A.,Budisa, N.,Waudby, C.A.,Beckmann, R.,Cassaignau, A.M.E.,Cabrita, L.D.,Christodoulou, J.
Modulating co-translational protein folding by rational design and ribosome engineering.
Nat Commun, 13:4243-4243, 2022

PubMed Abstract: Co-translational folding is a fundamental process for the efficient biosynthesis of nascent polypeptides that emerge through the ribosome exit tunnel. To understand how this process is modulated by the shape and surface of the narrow tunnel, we have rationally engineered three exit tunnel protein loops (uL22, uL23 and uL24) of the 70S ribosome by CRISPR/Cas9 gene editing, and studied the co-translational folding of an immunoglobulin-like filamin domain (FLN5). Our thermodynamics measurements employing F/N/methyl-TROSY NMR spectroscopy together with cryo-EM and molecular dynamics simulations reveal how the variations in the lengths of the loops present across species exert their distinct effects on the free energy of FLN5 folding. A concerted interplay of the uL23 and uL24 loops is sufficient to alter co-translational folding energetics, which we highlight by the opposite folding outcomes resulting from their extensions. These subtle modulations occur through a combination of the steric effects relating to the shape of the tunnel, the dynamic interactions between the ribosome surface and the unfolded nascent chain, and its altered exit pathway within the vestibule. These results illustrate the role of the exit tunnel structure in co-translational folding, and provide principles for how to remodel it to elicit a desired folding outcome.

PubMed: 35869078
DOI: 10.1038/s41467-022-31906-z

実験手法

ELECTRON MICROSCOPY (2.75 Å)