Cargando…
Structure and evolution of the 4-helix bundle domain of Zuotin, a J-domain protein co-chaperone of Hsp70
The J-domain protein Zuotin is a multi-domain eukaryotic Hsp70 co-chaperone. Though it is primarily ribosome-associated, positioned at the exit of the 60S subunit tunnel where it promotes folding of nascent polypeptide chains, Zuotin also has off-ribosome functions. Domains of Zuotin needed for 60S...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519820/ https://www.ncbi.nlm.nih.gov/pubmed/31091298 http://dx.doi.org/10.1371/journal.pone.0217098 |
_version_ | 1783418670751416320 |
---|---|
author | Shrestha, Om Kumar Sharma, Ruchika Tomiczek, Bartlomiej Lee, Woonghee Tonelli, Marco Cornilescu, Gabriel Stolarska, Milena Nierzwicki, Lukasz Czub, Jacek Markley, John L. Marszalek, Jaroslaw Ciesielski, Szymon J. Craig, Elizabeth A. |
author_facet | Shrestha, Om Kumar Sharma, Ruchika Tomiczek, Bartlomiej Lee, Woonghee Tonelli, Marco Cornilescu, Gabriel Stolarska, Milena Nierzwicki, Lukasz Czub, Jacek Markley, John L. Marszalek, Jaroslaw Ciesielski, Szymon J. Craig, Elizabeth A. |
author_sort | Shrestha, Om Kumar |
collection | PubMed |
description | The J-domain protein Zuotin is a multi-domain eukaryotic Hsp70 co-chaperone. Though it is primarily ribosome-associated, positioned at the exit of the 60S subunit tunnel where it promotes folding of nascent polypeptide chains, Zuotin also has off-ribosome functions. Domains of Zuotin needed for 60S association and interaction with Hsp70 are conserved in eukaryotes. However, whether the 4-helix bundle (4HB) domain is conserved remains an open question. We undertook evolutionary and structural approaches to clarify this issue. We found that the 4HB segment of human Zuotin also forms a bundle of 4 helices. The positive charge of Helix I, which in Saccharomyces cerevisiae is responsible for interaction with the 40S subunit, is particularly conserved. However, the C-termini of fungal and human 4HBs are not similar. In fungi the C-terminal segment forms a plug that folds back into the bundle; in S. cerevisiae it plays an important role in bundle stability and, off the ribosome, in transcriptional activation. In human, C-terminal helix IV of the 4HB is extended, protruding from the bundle. This extension serves as a linker to the regulatory SANT domains, which are present in animals, plants and protists, but not fungi. Further analysis of Zuotin sequences revealed that the plug likely arose as a result of genomic rearrangement upon SANT domain loss early in the fungal lineage. In the lineage leading to S. cerevisiae, the 4HB was subjected to positive selection with the plug becoming increasingly hydrophobic. Eventually, these hydrophobic plug residues were coopted for a novel regulatory function—activation of a recently emerged transcription factor, Pdr1. Our data suggests that Zuotin evolved off-ribosome functions twice—once involving SANT domains, then later in fungi, after SANT domain loss, by coopting the hydrophobic plug. Zuotin serves as an example of complex intertwining of molecular chaperone function and cell regulation. |
format | Online Article Text |
id | pubmed-6519820 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-65198202019-05-31 Structure and evolution of the 4-helix bundle domain of Zuotin, a J-domain protein co-chaperone of Hsp70 Shrestha, Om Kumar Sharma, Ruchika Tomiczek, Bartlomiej Lee, Woonghee Tonelli, Marco Cornilescu, Gabriel Stolarska, Milena Nierzwicki, Lukasz Czub, Jacek Markley, John L. Marszalek, Jaroslaw Ciesielski, Szymon J. Craig, Elizabeth A. PLoS One Research Article The J-domain protein Zuotin is a multi-domain eukaryotic Hsp70 co-chaperone. Though it is primarily ribosome-associated, positioned at the exit of the 60S subunit tunnel where it promotes folding of nascent polypeptide chains, Zuotin also has off-ribosome functions. Domains of Zuotin needed for 60S association and interaction with Hsp70 are conserved in eukaryotes. However, whether the 4-helix bundle (4HB) domain is conserved remains an open question. We undertook evolutionary and structural approaches to clarify this issue. We found that the 4HB segment of human Zuotin also forms a bundle of 4 helices. The positive charge of Helix I, which in Saccharomyces cerevisiae is responsible for interaction with the 40S subunit, is particularly conserved. However, the C-termini of fungal and human 4HBs are not similar. In fungi the C-terminal segment forms a plug that folds back into the bundle; in S. cerevisiae it plays an important role in bundle stability and, off the ribosome, in transcriptional activation. In human, C-terminal helix IV of the 4HB is extended, protruding from the bundle. This extension serves as a linker to the regulatory SANT domains, which are present in animals, plants and protists, but not fungi. Further analysis of Zuotin sequences revealed that the plug likely arose as a result of genomic rearrangement upon SANT domain loss early in the fungal lineage. In the lineage leading to S. cerevisiae, the 4HB was subjected to positive selection with the plug becoming increasingly hydrophobic. Eventually, these hydrophobic plug residues were coopted for a novel regulatory function—activation of a recently emerged transcription factor, Pdr1. Our data suggests that Zuotin evolved off-ribosome functions twice—once involving SANT domains, then later in fungi, after SANT domain loss, by coopting the hydrophobic plug. Zuotin serves as an example of complex intertwining of molecular chaperone function and cell regulation. Public Library of Science 2019-05-15 /pmc/articles/PMC6519820/ /pubmed/31091298 http://dx.doi.org/10.1371/journal.pone.0217098 Text en © 2019 Shrestha et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Shrestha, Om Kumar Sharma, Ruchika Tomiczek, Bartlomiej Lee, Woonghee Tonelli, Marco Cornilescu, Gabriel Stolarska, Milena Nierzwicki, Lukasz Czub, Jacek Markley, John L. Marszalek, Jaroslaw Ciesielski, Szymon J. Craig, Elizabeth A. Structure and evolution of the 4-helix bundle domain of Zuotin, a J-domain protein co-chaperone of Hsp70 |
title | Structure and evolution of the 4-helix bundle domain of Zuotin, a J-domain protein co-chaperone of Hsp70 |
title_full | Structure and evolution of the 4-helix bundle domain of Zuotin, a J-domain protein co-chaperone of Hsp70 |
title_fullStr | Structure and evolution of the 4-helix bundle domain of Zuotin, a J-domain protein co-chaperone of Hsp70 |
title_full_unstemmed | Structure and evolution of the 4-helix bundle domain of Zuotin, a J-domain protein co-chaperone of Hsp70 |
title_short | Structure and evolution of the 4-helix bundle domain of Zuotin, a J-domain protein co-chaperone of Hsp70 |
title_sort | structure and evolution of the 4-helix bundle domain of zuotin, a j-domain protein co-chaperone of hsp70 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519820/ https://www.ncbi.nlm.nih.gov/pubmed/31091298 http://dx.doi.org/10.1371/journal.pone.0217098 |
work_keys_str_mv | AT shresthaomkumar structureandevolutionofthe4helixbundledomainofzuotinajdomainproteincochaperoneofhsp70 AT sharmaruchika structureandevolutionofthe4helixbundledomainofzuotinajdomainproteincochaperoneofhsp70 AT tomiczekbartlomiej structureandevolutionofthe4helixbundledomainofzuotinajdomainproteincochaperoneofhsp70 AT leewoonghee structureandevolutionofthe4helixbundledomainofzuotinajdomainproteincochaperoneofhsp70 AT tonellimarco structureandevolutionofthe4helixbundledomainofzuotinajdomainproteincochaperoneofhsp70 AT cornilescugabriel structureandevolutionofthe4helixbundledomainofzuotinajdomainproteincochaperoneofhsp70 AT stolarskamilena structureandevolutionofthe4helixbundledomainofzuotinajdomainproteincochaperoneofhsp70 AT nierzwickilukasz structureandevolutionofthe4helixbundledomainofzuotinajdomainproteincochaperoneofhsp70 AT czubjacek structureandevolutionofthe4helixbundledomainofzuotinajdomainproteincochaperoneofhsp70 AT markleyjohnl structureandevolutionofthe4helixbundledomainofzuotinajdomainproteincochaperoneofhsp70 AT marszalekjaroslaw structureandevolutionofthe4helixbundledomainofzuotinajdomainproteincochaperoneofhsp70 AT ciesielskiszymonj structureandevolutionofthe4helixbundledomainofzuotinajdomainproteincochaperoneofhsp70 AT craigelizabetha structureandevolutionofthe4helixbundledomainofzuotinajdomainproteincochaperoneofhsp70 |