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Amino acid substrates impose polyamine, eIF5A, or hypusine requirement for peptide synthesis

Whereas ribosomes efficiently catalyze peptide bond synthesis by most amino acids, the imino acid proline is a poor substrate for protein synthesis. Previous studies have shown that the translation factor eIF5A and its bacterial ortholog EF-P bind in the E site of the ribosome where they contact the...

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Autores principales: Shin, Byung-Sik, Katoh, Takayuki, Gutierrez, Erik, Kim, Joo-Ran, Suga, Hiroaki, Dever, Thomas E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737446/
https://www.ncbi.nlm.nih.gov/pubmed/28637321
http://dx.doi.org/10.1093/nar/gkx532
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author Shin, Byung-Sik
Katoh, Takayuki
Gutierrez, Erik
Kim, Joo-Ran
Suga, Hiroaki
Dever, Thomas E.
author_facet Shin, Byung-Sik
Katoh, Takayuki
Gutierrez, Erik
Kim, Joo-Ran
Suga, Hiroaki
Dever, Thomas E.
author_sort Shin, Byung-Sik
collection PubMed
description Whereas ribosomes efficiently catalyze peptide bond synthesis by most amino acids, the imino acid proline is a poor substrate for protein synthesis. Previous studies have shown that the translation factor eIF5A and its bacterial ortholog EF-P bind in the E site of the ribosome where they contact the peptidyl-tRNA in the P site and play a critical role in promoting the synthesis of polyproline peptides. Using misacylated Pro-tRNA(Phe) and Phe-tRNA(Pro), we show that the imino acid proline and not tRNA(Pro) imposes the primary eIF5A requirement for polyproline synthesis. Though most proline analogs require eIF5A for efficient peptide synthesis, azetidine-2-caboxylic acid, a more flexible four-membered ring derivative of proline, shows relaxed eIF5A dependency, indicating that the structural rigidity of proline might contribute to the requirement for eIF5A. Finally, we examine the interplay between eIF5A and polyamines in promoting translation elongation. We show that eIF5A can obviate the polyamine requirement for general translation elongation, and that this activity is independent of the conserved hypusine modification on eIF5A. Thus, we propose that the body of eIF5A functionally substitutes for polyamines to promote general protein synthesis and that the hypusine modification on eIF5A is critically important for poor substrates like proline.
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spelling pubmed-57374462018-01-09 Amino acid substrates impose polyamine, eIF5A, or hypusine requirement for peptide synthesis Shin, Byung-Sik Katoh, Takayuki Gutierrez, Erik Kim, Joo-Ran Suga, Hiroaki Dever, Thomas E. Nucleic Acids Res Molecular Biology Whereas ribosomes efficiently catalyze peptide bond synthesis by most amino acids, the imino acid proline is a poor substrate for protein synthesis. Previous studies have shown that the translation factor eIF5A and its bacterial ortholog EF-P bind in the E site of the ribosome where they contact the peptidyl-tRNA in the P site and play a critical role in promoting the synthesis of polyproline peptides. Using misacylated Pro-tRNA(Phe) and Phe-tRNA(Pro), we show that the imino acid proline and not tRNA(Pro) imposes the primary eIF5A requirement for polyproline synthesis. Though most proline analogs require eIF5A for efficient peptide synthesis, azetidine-2-caboxylic acid, a more flexible four-membered ring derivative of proline, shows relaxed eIF5A dependency, indicating that the structural rigidity of proline might contribute to the requirement for eIF5A. Finally, we examine the interplay between eIF5A and polyamines in promoting translation elongation. We show that eIF5A can obviate the polyamine requirement for general translation elongation, and that this activity is independent of the conserved hypusine modification on eIF5A. Thus, we propose that the body of eIF5A functionally substitutes for polyamines to promote general protein synthesis and that the hypusine modification on eIF5A is critically important for poor substrates like proline. Oxford University Press 2017-08-21 2017-06-16 /pmc/articles/PMC5737446/ /pubmed/28637321 http://dx.doi.org/10.1093/nar/gkx532 Text en Published by Oxford University Press on behalf of Nucleic Acids Research 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.
spellingShingle Molecular Biology
Shin, Byung-Sik
Katoh, Takayuki
Gutierrez, Erik
Kim, Joo-Ran
Suga, Hiroaki
Dever, Thomas E.
Amino acid substrates impose polyamine, eIF5A, or hypusine requirement for peptide synthesis
title Amino acid substrates impose polyamine, eIF5A, or hypusine requirement for peptide synthesis
title_full Amino acid substrates impose polyamine, eIF5A, or hypusine requirement for peptide synthesis
title_fullStr Amino acid substrates impose polyamine, eIF5A, or hypusine requirement for peptide synthesis
title_full_unstemmed Amino acid substrates impose polyamine, eIF5A, or hypusine requirement for peptide synthesis
title_short Amino acid substrates impose polyamine, eIF5A, or hypusine requirement for peptide synthesis
title_sort amino acid substrates impose polyamine, eif5a, or hypusine requirement for peptide synthesis
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737446/
https://www.ncbi.nlm.nih.gov/pubmed/28637321
http://dx.doi.org/10.1093/nar/gkx532
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