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New mechanisms controlling the positioning and activity of the ParABS chromosome partition system
DNA segregation is a central process in biology which ensures that every daughter cell receives the full complement of genetic information upon cell division. In bacteria, the most widespread mechanism to segregate DNA is the tripartite ParABS system. It includes a DNA-binding protein named ParB,...
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| Formatua: | Dissertation |
| Hizkuntza: | ingelesa |
| Argitaratua: |
Philipps-Universität Marburg
2021
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| Sarrera elektronikoa: | PDF testu osoa |
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| Gaia: | DNA segregation is a central process in biology which ensures that every daughter cell receives the full
complement of genetic information upon cell division. In bacteria, the most widespread mechanism
to segregate DNA is the tripartite ParABS system. It includes a DNA-binding protein named ParB, which
interacts with centromere-like parS sequences typically located close to the origin of replication. After
initial binding to parS, ParB spreads to adjacent DNA regions, giving rise to a large nucleoprotein
complex known as the partition complex. It then interacts dynamically with the third component of
the ParABS system, the P-loop ATPase ParA, which directs the progressive movement of the partition
complex towards opposite cell poles by a ratchet-like mechanism.
The ParABS system is often organized by polar landmarks that anchor the origin of replication at
specific locations within the cell and sequester free ParA, likely enhancing the robustness of the
segregation process. In this work, we identify the bactofilin cytoskeleton as a new organizer of the
ParABS DNA-segregation machinery in Myxococcus xanthus. We show that the ParBS partition complex
associates with the pole-distal ends of the bactofilin filaments, whereas ParA binds along their entire
length, recruited by the ParB-like protein PadC.
Structural studies of PadC revealed that the ParB/Srx domain of this protein functions as a nucleotidebinding
domain that specifically interacts with the ribonucleotide CTP. CTP-binding keeps the ParB/Srx
domain of PadC in a closed-dimer conformation that is necessary for the interaction with ParA.
Remarkably, we show that CTP-binding is conserved in ParB. In this protein, the CTP-dependent
dimerization of the N-terminal ParB/Srx domain is catalyzed by parS. In contrast to PadC, ParB exhibits
CTPase activity. We show that CTP binding and hydrolysis are necessary for partition complex
formation and function. Our results identify ParB homologues as a new class of nucleotide switches
that use CTP instead of ATP or GTP and thus, open the possibility that CTP could regulate the function
of other protein families.
In addition to its role in chromosome segregation, ParB participates in cell division in Caulobacter
crescentus by recruiting the negative regulator of FtsZ polymerization, MipZ, to the cell poles, thereby
limiting the assembly of the cytokinetic FtsZ ring to the midcell region. In this study, we show that the
MipZ system is conserved in alphaproteobacteria. However, the mechanisms by which it regulates cell
division might have adapted to the specific needs of the host organism. |
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| Deskribapen fisikoa: | 208 Seiten |
| DOI: | 10.17192/z2021.0077 |