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FtsZ filament structures in different nucleotide states reveal the mechanism of assembly dynamics
Treadmilling protein filaments perform essential cellular functions by growing from one end while shrinking from the other, driven by nucleotide hydrolysis. Bacterial cell division relies on the primitive tubulin homolog FtsZ, a target for antibiotic discovery that assembles into single treadmilling...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8936486/ https://www.ncbi.nlm.nih.gov/pubmed/35312677 http://dx.doi.org/10.1371/journal.pbio.3001497 |
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author | Ruiz, Federico M. Huecas, Sonia Santos-Aledo, Alicia Prim, Elena A. Andreu, José M. Fernández-Tornero, Carlos |
author_facet | Ruiz, Federico M. Huecas, Sonia Santos-Aledo, Alicia Prim, Elena A. Andreu, José M. Fernández-Tornero, Carlos |
author_sort | Ruiz, Federico M. |
collection | PubMed |
description | Treadmilling protein filaments perform essential cellular functions by growing from one end while shrinking from the other, driven by nucleotide hydrolysis. Bacterial cell division relies on the primitive tubulin homolog FtsZ, a target for antibiotic discovery that assembles into single treadmilling filaments that hydrolyse GTP at an active site formed upon subunit association. We determined high-resolution filament structures of FtsZ from the pathogen Staphylococcus aureus in complex with different nucleotide analogs and cations, including mimetics of the ground and transition states of catalysis. Together with mutational and biochemical analyses, our structures reveal interactions made by the GTP γ-phosphate and Mg(2+) at the subunit interface, a K(+) ion stabilizing loop T7 for co-catalysis, new roles of key residues at the active site and a nearby crosstalk area, and rearrangements of a dynamic water shell bridging adjacent subunits upon GTP hydrolysis. We propose a mechanistic model that integrates nucleotide hydrolysis signaling with assembly-associated conformational changes and filament treadmilling. Equivalent assembly mechanisms may apply to more complex tubulin and actin cytomotive filaments that share analogous features with FtsZ. |
format | Online Article Text |
id | pubmed-8936486 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-89364862022-03-22 FtsZ filament structures in different nucleotide states reveal the mechanism of assembly dynamics Ruiz, Federico M. Huecas, Sonia Santos-Aledo, Alicia Prim, Elena A. Andreu, José M. Fernández-Tornero, Carlos PLoS Biol Research Article Treadmilling protein filaments perform essential cellular functions by growing from one end while shrinking from the other, driven by nucleotide hydrolysis. Bacterial cell division relies on the primitive tubulin homolog FtsZ, a target for antibiotic discovery that assembles into single treadmilling filaments that hydrolyse GTP at an active site formed upon subunit association. We determined high-resolution filament structures of FtsZ from the pathogen Staphylococcus aureus in complex with different nucleotide analogs and cations, including mimetics of the ground and transition states of catalysis. Together with mutational and biochemical analyses, our structures reveal interactions made by the GTP γ-phosphate and Mg(2+) at the subunit interface, a K(+) ion stabilizing loop T7 for co-catalysis, new roles of key residues at the active site and a nearby crosstalk area, and rearrangements of a dynamic water shell bridging adjacent subunits upon GTP hydrolysis. We propose a mechanistic model that integrates nucleotide hydrolysis signaling with assembly-associated conformational changes and filament treadmilling. Equivalent assembly mechanisms may apply to more complex tubulin and actin cytomotive filaments that share analogous features with FtsZ. Public Library of Science 2022-03-21 /pmc/articles/PMC8936486/ /pubmed/35312677 http://dx.doi.org/10.1371/journal.pbio.3001497 Text en © 2022 Ruiz et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://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 Ruiz, Federico M. Huecas, Sonia Santos-Aledo, Alicia Prim, Elena A. Andreu, José M. Fernández-Tornero, Carlos FtsZ filament structures in different nucleotide states reveal the mechanism of assembly dynamics |
title | FtsZ filament structures in different nucleotide states reveal the mechanism of assembly dynamics |
title_full | FtsZ filament structures in different nucleotide states reveal the mechanism of assembly dynamics |
title_fullStr | FtsZ filament structures in different nucleotide states reveal the mechanism of assembly dynamics |
title_full_unstemmed | FtsZ filament structures in different nucleotide states reveal the mechanism of assembly dynamics |
title_short | FtsZ filament structures in different nucleotide states reveal the mechanism of assembly dynamics |
title_sort | ftsz filament structures in different nucleotide states reveal the mechanism of assembly dynamics |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8936486/ https://www.ncbi.nlm.nih.gov/pubmed/35312677 http://dx.doi.org/10.1371/journal.pbio.3001497 |
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