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Slowest-first protein translation scheme: Structural asymmetry and co-translational folding

Proteins are translated from the N to the C terminus, raising the basic question of how this innate directionality affects their evolution. To explore this question, we analyze 16,200 structures from the Protein Data Bank (PDB). We find remarkable enrichment of α helices at the C terminus and β stra...

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Detalles Bibliográficos
Autores principales: McBride, John M., Tlusty, Tsvi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Biophysical Society 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8715247/
https://www.ncbi.nlm.nih.gov/pubmed/34813729
http://dx.doi.org/10.1016/j.bpj.2021.11.024
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author McBride, John M.
Tlusty, Tsvi
author_facet McBride, John M.
Tlusty, Tsvi
author_sort McBride, John M.
collection PubMed
description Proteins are translated from the N to the C terminus, raising the basic question of how this innate directionality affects their evolution. To explore this question, we analyze 16,200 structures from the Protein Data Bank (PDB). We find remarkable enrichment of α helices at the C terminus and β strands at the N terminus. Furthermore, this [Formula: see text] asymmetry correlates with sequence length and contact order, both determinants of folding rate, hinting at possible links to co-translational folding (CTF). Hence, we propose the “slowest-first” scheme, whereby protein sequences evolved structural asymmetry to accelerate CTF: the slowest of the cooperatively folding segments are positioned near the N terminus so they have more time to fold during translation. A phenomenological model predicts that CTF can be accelerated by asymmetry in folding rate, up to double the rate, when folding time is commensurate with translation time; analysis of the PDB predicts that structural asymmetry is indeed maximal in this regime. This correspondence is greater in prokaryotes, which generally require faster protein production. Altogether, this indicates that accelerating CTF is a substantial evolutionary force whose interplay with stability and functionality is encoded in secondary structure asymmetry.
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spelling pubmed-87152472022-12-21 Slowest-first protein translation scheme: Structural asymmetry and co-translational folding McBride, John M. Tlusty, Tsvi Biophys J Articles Proteins are translated from the N to the C terminus, raising the basic question of how this innate directionality affects their evolution. To explore this question, we analyze 16,200 structures from the Protein Data Bank (PDB). We find remarkable enrichment of α helices at the C terminus and β strands at the N terminus. Furthermore, this [Formula: see text] asymmetry correlates with sequence length and contact order, both determinants of folding rate, hinting at possible links to co-translational folding (CTF). Hence, we propose the “slowest-first” scheme, whereby protein sequences evolved structural asymmetry to accelerate CTF: the slowest of the cooperatively folding segments are positioned near the N terminus so they have more time to fold during translation. A phenomenological model predicts that CTF can be accelerated by asymmetry in folding rate, up to double the rate, when folding time is commensurate with translation time; analysis of the PDB predicts that structural asymmetry is indeed maximal in this regime. This correspondence is greater in prokaryotes, which generally require faster protein production. Altogether, this indicates that accelerating CTF is a substantial evolutionary force whose interplay with stability and functionality is encoded in secondary structure asymmetry. The Biophysical Society 2021-12-21 2021-11-20 /pmc/articles/PMC8715247/ /pubmed/34813729 http://dx.doi.org/10.1016/j.bpj.2021.11.024 Text en © 2021 Biophysical Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Articles
McBride, John M.
Tlusty, Tsvi
Slowest-first protein translation scheme: Structural asymmetry and co-translational folding
title Slowest-first protein translation scheme: Structural asymmetry and co-translational folding
title_full Slowest-first protein translation scheme: Structural asymmetry and co-translational folding
title_fullStr Slowest-first protein translation scheme: Structural asymmetry and co-translational folding
title_full_unstemmed Slowest-first protein translation scheme: Structural asymmetry and co-translational folding
title_short Slowest-first protein translation scheme: Structural asymmetry and co-translational folding
title_sort slowest-first protein translation scheme: structural asymmetry and co-translational folding
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8715247/
https://www.ncbi.nlm.nih.gov/pubmed/34813729
http://dx.doi.org/10.1016/j.bpj.2021.11.024
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