ParB-type DNA segregation proteins are CTP-dependent molecular switches, M. Osorio-Valeriano (a,b), F. Altegoer (c,d), W. Steinchen (c,d), S. Urban (a), Y. Liu (a), G. Bange (c,d) and M. Thanbichler (a,b,d),
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Microbiology, Marburg (Germany) (c) Department of Chemistry, University of Marburg (Germany) (d) Center for Synthetic Microbiology (SYNMIKRO), Marburg (Germany)
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STRUCTURE-FUNCTION APPROACH IDENTIFIES AtFKBP53 TO BE A CHIMERIC CHAPERONE
X-ray crystallography, small-angle X-ray scattering (SAXS), and functional analyses revealed Arabidopsis thaliana FKBP53 to be a chimeric chaperone with an N-terminal nucleoplasmin domain and a C-terminal peptidyl- prolyl isomerase (PPIase) domain. The protein adopts a pentapus-like structure with a pentameric core, five long arms and terminal PPIase domains.
PRINCIPAL PUBLICATION AND AUTHORS
from its initial target site and thus allows the loading of additional ParB rings, giving rise to the aforementioned partition complexes that recruit ParA for effective DNA segregation. Ring formation primes ParB for CTP hydrolysis, which eventually leads to the disengagement of the ParB/Srx domains and the release of ParB from the DNA, thereby limiting ParB rings to the parS-proximal regions of the chromosome.
The present study shows that ParB-like proteins are part of a previously neglected class of nucleotide-dependent molecular switches that use the pyrimidine nucleotide CTP instead of ATP or GTP to control biological processes. These results provide a new perspective on bacterial chromosome segregation and pave the way for a broader perception of CTP-dependent regulatory pathways in biological systems.
In the small nuclear space of a eukaryotic cell, the several-metres-long DNA gets accommodated by organising into a higher order structure called chromatin, which has nucleosomes as its basic repeating units. Two copies each of the positively charged core histones H2A, H2B, H3, and H4, and a negatively charged DNA of about 146 base-pair length, get assembled to form a nucleosome core. Once the DNA is organised into a nucleosome, it creates a barrier for various significant DNA-dependent cellular processes such as transcription, replication and DNA repair. Several remodellers and histone chaperones thus enable timely nucleosome assembly and disassembly, by depositing and evicting histones, thereby eliciting a control on DNA-related processes. Nucleoplasmins are the first known molecular chaperones and they actively deposit histone H2A/H2B and H3/H4 onto the DNA. Nucleoplasmins are known from different organisms and, although they share very little sequence identity, they all have a similar structural organisation, forming a stable pentamer. Due to poor sequence identity amongst nucleoplasmins, and due to a lack of structural information, nucleoplasmins were
thought to be absent in plants. The possibility of plants having nucleoplasmins was therefore suggested much later , with AtFKBP53 being named as a nucleoplasmin-FKBP. The acidic N-terminal region of AtFKBP53 was already reported to interact with histone H3 and regulate the ribosomal RNA gene expression . The study also shows that the C-terminal FK506- binding domain is not important for histone interaction. Taken together, it thus appears that the histone interaction of AtFKBP53 is due to the N-terminal nucleoplasmin domain and that the C-terminal domain has an independent function.
A 2.4-Å diffraction dataset was collected from a crystal of the AtFKBP53 N-terminal domain (NTD) at beamline BM14. The resulting crystal structure revealed it to form a pentameric barrel (Figure 23a), in which each monomer possesses an eight-stranded beta-sandwich fold (Figure 23b) that is characteristic of nucleoplasmin family members. SAXS data for AtFKBP53 NTD were collected at beamline BM29. The ab initio average model from SAXS neatly fitted the experimental data and showed a good fit with the crystal structure