Dynamic Enzyme Docking to the Ribosome Coordinates N-terminal Processing with Polypeptide Folding

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2013 Jun 18

PMID 23770820

Citations 31

Authors

Arzu Sandikci

Felix Gloge

Michael Martinez

Matthias P Mayer

Rebecca Wade

Bernd Bukau

Gunter Kramer

Affiliations

Soon will be listed here.

Abstract

Newly synthesized polypeptides undergo various cotranslational maturation steps, including N-terminal enzymatic processing, chaperone-assisted folding and membrane targeting, but the spatial and temporal coordination of these steps is unclear. We show that Escherichia coli methionine aminopeptidase (MAP) associates with ribosomes through a charged loop that is crucial for nascent-chain processing and cell viability. MAP competes with peptide deformylase (PDF), the first enzyme to act on nascent chains, for binding sites at the ribosomal tunnel exit. PDF has extremely fast association and dissociation kinetics, which allows it to frequently sample ribosomes and ensure the processing of nascent chains after their emergence. Premature recruitment of the chaperone trigger factor, or polypeptide folding, negatively affect processing efficiency. Thus, the fast ribosome association kinetics of PDF and MAP are crucial for the temporal separation of nascent-chain processing from later maturation events, including chaperone recruitment and folding.

Citing Articles

Destined for destruction: The role of methionine aminopeptidases and plant cysteine oxidases in N-degron formation.

Fuentes-Terron A, Latter R, Madden S, Manrique-Gil I, Estrada J, Arteaga N Plant Physiol. 2025; 197(1).

PMID: 39875105 PMC: 11773813. DOI: 10.1093/plphys/kiae667.

NAC guides a ribosomal multienzyme complex for nascent protein processing.

Lentzsch A, Yudin D, Gamerdinger M, Chandrasekar S, Rabl L, Scaiola A Nature. 2024; 633(8030):718-724.

PMID: 39169182 DOI: 10.1038/s41586-024-07846-7.

Bayesian reweighting of biomolecular structural ensembles using heterogeneous cryo-EM maps with the cryoENsemble method.

Wlodarski T, Streit J, Mitropoulou A, Cabrita L, Vendruscolo M, Christodoulou J Sci Rep. 2024; 14(1):18149.

PMID: 39103467 PMC: 11300795. DOI: 10.1038/s41598-024-68468-7.

The dynamic architecture of Map1- and NatB-ribosome complexes coordinates the sequential modifications of nascent polypeptide chains.

Knorr A, Mackens-Kiani T, Musial J, Berninghausen O, Becker T, Beatrix B PLoS Biol. 2023; 21(4):e3001995.

PMID: 37079644 PMC: 10118133. DOI: 10.1371/journal.pbio.3001995.

Dependence of diffusion in cytoplasm on protein size, environmental conditions, and cell growth.

Bellotto N, Agudo-Canalejo J, Colin R, Golestanian R, Malengo G, Sourjik V Elife. 2022; 11.

PMID: 36468683 PMC: 9810338. DOI: 10.7554/eLife.82654.

References

Merz F, Boehringer D, Schaffitzel C, Preissler S, Hoffmann A, Maier T . Molecular mechanism and structure of Trigger Factor bound to the translating ribosome. EMBO J. 2008; 27(11):1622-32. PMC: 2426727. DOI: 10.1038/emboj.2008.89. View

Dolinsky T, Czodrowski P, Li H, Nielsen J, Jensen J, Klebe G . PDB2PQR: expanding and upgrading automated preparation of biomolecular structures for molecular simulations. Nucleic Acids Res. 2007; 35(Web Server issue):W522-5. PMC: 1933214. DOI: 10.1093/nar/gkm276. View

Datsenko K, Wanner B . One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci U S A. 2000; 97(12):6640-5. PMC: 18686. DOI: 10.1073/pnas.120163297. View

Grudnik P, Bange G, Sinning I . Protein targeting by the signal recognition particle. Biol Chem. 2009; 390(8):775-82. DOI: 10.1515/BC.2009.102. View

LINK A, Robison K, Church G . Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12. Electrophoresis. 1997; 18(8):1259-313. DOI: 10.1002/elps.1150180807. View

Groche D, Becker A, Schlichting I, Kabsch W, Schultz S, Wagner A . Isolation and crystallization of functionally competent Escherichia coli peptide deformylase forms containing either iron or nickel in the active site. Biochem Biophys Res Commun. 1998; 246(2):342-6. DOI: 10.1006/bbrc.1998.8616. View

Holtkamp W, Lee S, Bornemann T, Senyushkina T, Rodnina M, Wintermeyer W . Dynamic switch of the signal recognition particle from scanning to targeting. Nat Struct Mol Biol. 2012; 19(12):1332-7. DOI: 10.1038/nsmb.2421. View

Rutkowska A, Beerbaum M, Rajagopalan N, Fiaux J, Schmieder P, Kramer G . Large-scale purification of ribosome-nascent chain complexes for biochemical and structural studies. FEBS Lett. 2009; 583(14):2407-13. DOI: 10.1016/j.febslet.2009.06.041. View

Agashe V, Guha S, Chang H, Genevaux P, Hayer-Hartl M, Stemp M . Function of trigger factor and DnaK in multidomain protein folding: increase in yield at the expense of folding speed. Cell. 2004; 117(2):199-209. DOI: 10.1016/s0092-8674(04)00299-5. View

10.

Andreasson C, Fiaux J, Rampelt H, Mayer M, Bukau B . Hsp110 is a nucleotide-activated exchange factor for Hsp70. J Biol Chem. 2008; 283(14):8877-84. DOI: 10.1074/jbc.M710063200. View

11.

Housman D, Gillespie D, Lodish H . Removal of formyl-methionine residue from nascent bacteriophage f2 protein. J Mol Biol. 1972; 65(1):163-6. DOI: 10.1016/0022-2836(72)90498-6. View

12.

Pine M . Kinetics of maturation of the amino termini of the cell proteins of Escherichia coli. Biochim Biophys Acta. 1969; 174(1):359-72. DOI: 10.1016/0005-2787(69)90261-5. View

13.

Hartl F, Bracher A, Hayer-Hartl M . Molecular chaperones in protein folding and proteostasis. Nature. 2011; 475(7356):324-32. DOI: 10.1038/nature10317. View

14.

Deuerling E, Tomoyasu T, Mogk A, Bukau B . Trigger factor and DnaK cooperate in folding of newly synthesized proteins. Nature. 1999; 400(6745):693-6. DOI: 10.1038/23301. View

15.

Bingel-Erlenmeyer R, Kohler R, Kramer G, Sandikci A, Antolic S, Maier T . A peptide deformylase-ribosome complex reveals mechanism of nascent chain processing. Nature. 2008; 452(7183):108-11. DOI: 10.1038/nature06683. View

16.

Bhushan S, Hoffmann T, Seidelt B, Frauenfeld J, Mielke T, Berninghausen O . SecM-stalled ribosomes adopt an altered geometry at the peptidyl transferase center. PLoS Biol. 2011; 9(1):e1000581. PMC: 3022528. DOI: 10.1371/journal.pbio.1000581. View

17.

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

18.

Kramer G, Rauch T, Rist W, Vorderwulbecke S, Patzelt H, Schulze-Specking A . L23 protein functions as a chaperone docking site on the ribosome. Nature. 2002; 419(6903):171-4. DOI: 10.1038/nature01047. View

19.

Milligan D, Koshland Jr D . The amino terminus of the aspartate chemoreceptor is formylmethionine. J Biol Chem. 1990; 265(8):4455-60. View

20.

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