The Ribosome Modulates Folding Inside the Ribosomal Exit Tunnel

Overview

Journal Commun Biol

Specialty Biology

Date 2021 May 6

PMID 33953328

Citations 23

Authors

Florian Wruck

Pengfei Tian

Renuka Kudva

Robert B Best

Gunnar von Heijne

Sander J Tans

Alexandros Katranidis

Affiliations

Soon will be listed here.

Abstract

Proteins commonly fold co-translationally at the ribosome, while the nascent chain emerges from the ribosomal exit tunnel. Protein domains that are sufficiently small can even fold while still located inside the tunnel. However, the effect of the tunnel on the folding dynamics of these domains is not well understood. Here, we combine optical tweezers with single-molecule FRET and molecular dynamics simulations to investigate folding of the small zinc-finger domain ADR1a inside and at the vestibule of the ribosomal tunnel. The tunnel is found to accelerate folding and stabilize the folded state, reminiscent of the effects of chaperonins. However, a simple mechanism involving stabilization by confinement does not explain the results. Instead, it appears that electrostatic interactions between the protein and ribosome contribute to the observed folding acceleration and stabilization of ADR1a.

Citing Articles

Remodelled ribosomal populations synthesize a specific proteome in proliferating plant tissue during cold.

Martinez-Seidel F, Suwanchaikasem P, Gentry-Torfer D, Rajarathinam Y, Ebert A, Erban A Philos Trans R Soc Lond B Biol Sci. 2025; 380(1921):20230384.

PMID: 40045790 PMC: 11883437. DOI: 10.1098/rstb.2023.0384.

Role of Sec61α2 Translocon in Insulin Biosynthesis.

Xu X, Bell T, Le T, Zhao I, Walker E, Wang Y Diabetes. 2024; 73(12):2034-2044.

PMID: 39325584 PMC: 11579409. DOI: 10.2337/db24-0115.

Single-residue effects on the behavior of a nascent polypeptide chain inside the ribosome exit tunnel.

Pardo-Avila F, Kudva R, Levitt M, von Heijne G bioRxiv. 2024; .

PMID: 39229094 PMC: 11370347. DOI: 10.1101/2024.08.20.608737.

Ribosome Pausing Negatively Regulates Protein Translation in Maize Seedlings during Dark-to-Light Transitions.

Hou M, Fan W, Zhong D, Dai X, Wang Q, Liu W Int J Mol Sci. 2024; 25(14).

PMID: 39063227 PMC: 11277263. DOI: 10.3390/ijms25147985.

VeloPro: A pipeline integrating Ribo-seq and AlphaFold deciphers association patterns between translation velocity and protein structure features.

Bian B, Kumagai T, Saito Y Imeta. 2024; 2(4):e148.

PMID: 38868219 PMC: 10989810. DOI: 10.1002/imt2.148.

References

Wruck F, Katranidis A, Nierhaus K, Buldt G, Hegner M . Translation and folding of single proteins in real time. Proc Natl Acad Sci U S A. 2017; 114(22):E4399-E4407. PMC: 5465881. DOI: 10.1073/pnas.1617873114. View

Fedyukina D, Cavagnero S . Protein folding at the exit tunnel. Annu Rev Biophys. 2011; 40:337-59. PMC: 5807062. DOI: 10.1146/annurev-biophys-042910-155338. View

Sirur A, Knott M, Best R . Effect of interactions with the chaperonin cavity on protein folding and misfolding. Phys Chem Chem Phys. 2013; 16(14):6358-66. PMC: 4577569. DOI: 10.1039/c3cp52872c. View

Abe R, Shiraga K, Ebisu S, Takagi H, Hohsaka T . Incorporation of fluorescent non-natural amino acids into N-terminal tag of proteins in cell-free translation and its dependence on position and neighboring codons. J Biosci Bioeng. 2010; 110(1):32-8. DOI: 10.1016/j.jbiosc.2010.01.003. View

OBrien E, Hsu S, Christodoulou J, Vendruscolo M, Dobson C . Transient tertiary structure formation within the ribosome exit port. J Am Chem Soc. 2010; 132(47):16928-37. DOI: 10.1021/ja106530y. View

Kempf N, Remes C, Ledesch R, Zuchner T, Hofig H, Ritter I . A Novel Method to Evaluate Ribosomal Performance in Cell-Free Protein Synthesis Systems. Sci Rep. 2017; 7:46753. PMC: 5402277. DOI: 10.1038/srep46753. View

Bhushan S, Gartmann M, Halic M, Armache J, Jarasch A, Mielke T . alpha-Helical nascent polypeptide chains visualized within distinct regions of the ribosomal exit tunnel. Nat Struct Mol Biol. 2010; 17(3):313-7. DOI: 10.1038/nsmb.1756. View

Katranidis A, Atta D, Schlesinger R, Nierhaus K, Choli-Papadopoulou T, Gregor I . Fast biosynthesis of GFP molecules: a single-molecule fluorescence study. Angew Chem Int Ed Engl. 2009; 48(10):1758-61. DOI: 10.1002/anie.200806070. View

Kosolapov A, Deutsch C . Tertiary interactions within the ribosomal exit tunnel. Nat Struct Mol Biol. 2009; 16(4):405-11. PMC: 2670549. DOI: 10.1038/nsmb.1571. View

10.

Hegner M, Smith S, Bustamante C . Polymerization and mechanical properties of single RecA-DNA filaments. Proc Natl Acad Sci U S A. 1999; 96(18):10109-14. PMC: 17850. DOI: 10.1073/pnas.96.18.10109. View

11.

Kramer G, Ramachandiran V, Hardesty B . Cotranslational folding--omnia mea mecum porto?. Int J Biochem Cell Biol. 2001; 33(6):541-53. DOI: 10.1016/s1357-2725(01)00044-9. View

12.

Mittal J, Best R . Thermodynamics and kinetics of protein folding under confinement. Proc Natl Acad Sci U S A. 2008; 105(51):20233-8. PMC: 2629327. DOI: 10.1073/pnas.0807742105. View

13.

Zhou H, Dill K . Stabilization of proteins in confined spaces. Biochemistry. 2001; 40(38):11289-93. DOI: 10.1021/bi0155504. View

14.

Tu L, Khanna P, Deutsch C . Transmembrane segments form tertiary hairpins in the folding vestibule of the ribosome. J Mol Biol. 2013; 426(1):185-98. PMC: 3872176. DOI: 10.1016/j.jmb.2013.09.013. View

15.

Kemp G, Nilsson O, Tian P, Best R, von Heijne G . Cotranslational folding cooperativity of contiguous domains of α-spectrin. Proc Natl Acad Sci U S A. 2020; 117(25):14119-14126. PMC: 7322005. DOI: 10.1073/pnas.1909683117. View

16.

OBrien E, Christodoulou J, Vendruscolo M, Dobson C . New scenarios of protein folding can occur on the ribosome. J Am Chem Soc. 2011; 133(3):513-26. DOI: 10.1021/ja107863z. View

17.

Voss N, Gerstein M, Steitz T, Moore P . The geometry of the ribosomal polypeptide exit tunnel. J Mol Biol. 2006; 360(4):893-906. DOI: 10.1016/j.jmb.2006.05.023. View

18.

Kaiser C, Goldman D, Chodera J, Tinoco Jr I, Bustamante C . The ribosome modulates nascent protein folding. Science. 2011; 334(6063):1723-7. PMC: 4172366. DOI: 10.1126/science.1209740. View

19.

Cabrita L, Dobson C, Christodoulou J . Protein folding on the ribosome. Curr Opin Struct Biol. 2010; 20(1):33-45. DOI: 10.1016/j.sbi.2010.01.005. View

20.

Parraga G, Horvath S, Eisen A, TAYLOR W, Hood L, Young E . Zinc-dependent structure of a single-finger domain of yeast ADR1. Science. 1988; 241(4872):1489-92. DOI: 10.1126/science.3047872. View