6I0Y

TnaC-stalled ribosome complex with the titin I27 domain folding close to the ribosomal exit tunnel

Summary for 6I0Y

• Entry DOI: 10.2210/pdb6i0y/pdb
• EMDB information: 0322
• Descriptor: 50S ribosomal protein L24, 50S ribosomal protein L25, 23S ribosomal RNA, ... (40 entities in total)
• Functional Keywords: protein folding, ribosomal exit tunnel, nascent chain, titin i27 domain, ribosome
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 36
• Total formula weight: 1414237.80

Authors

Su, T.,Kudva, R.,von Heijne, G.,Beckmann, R. (deposition date: 2018-10-26, release date: 2018-12-05, Last modification date: 2024-10-23)

Primary citation

Tian, P.,Steward, A.,Kudva, R.,Su, T.,Shilling, P.J.,Nickson, A.A.,Hollins, J.J.,Beckmann, R.,von Heijne, G.,Clarke, J.,Best, R.B.
Folding pathway of an Ig domain is conserved on and off the ribosome.
Proc. Natl. Acad. Sci. U.S.A., 115:E11284-E11293, 2018

PubMed Abstract: Proteins that fold cotranslationally may do so in a restricted configurational space, due to the volume occupied by the ribosome. How does this environment, coupled with the close proximity of the ribosome, affect the folding pathway of a protein? Previous studies have shown that the cotranslational folding process for many proteins, including small, single domains, is directly affected by the ribosome. Here, we investigate the cotranslational folding of an all-β Ig domain, titin I27. Using an arrest peptide-based assay and structural studies by cryo-EM, we show that I27 folds in the mouth of the ribosome exit tunnel. Simulations that use a kinetic model for the force dependence of escape from arrest accurately predict the fraction of folded protein as a function of length. We used these simulations to probe the folding pathway on and off the ribosome. Our simulations-which also reproduce experiments on mutant forms of I27-show that I27 folds, while still sequestered in the mouth of the ribosome exit tunnel, by essentially the same pathway as free I27, with only subtle shifts of critical contacts from the C to the N terminus.

PubMed: 30413621
DOI: 10.1073/pnas.1810523115

Experimental method

ELECTRON MICROSCOPY (3.2 Å)