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A CTP-dependent gating mechanism enables ParB spreading on DNA

DOI: 10.7554/eLife.69676 DOI Help

Authors: Adam S. B. Jalal (John Innes Centre) , Ngat T. Tran (John Innes Centre) , Clare E. M. Stevenson (John Innes Centre) , Afroze Chimthanawala (Tata Institute of Fundamental Research; SASTRA University) , Anjana Badrinarayanan (Tata Institute of Fundamental Research) , David M. Lawson (John Innes Centre) , Tung B. K. Le (John Innes Centre)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Elife , VOL 10

State: Published (Approved)
Published: August 2021
Diamond Proposal Number(s): 13467 , 18565

Open Access Open Access

Abstract: Proper chromosome segregation is essential in all living organisms. The ParA-ParB-parS system is widely employed for chromosome segregation in bacteria. Previously, we showed that Caulobacter crescentus ParB requires cytidine triphosphate to escape the nucleation site parS and spread by sliding to the neighboring DNA (Jalal et al., 2020). Here, we provide the structural basis for this transition from nucleation to spreading by solving co-crystal structures of a C-terminal domain truncated C. crescentus ParB with parS and with a CTP analog. Nucleating ParB is an open clamp, in which parS is captured at the DNA-binding domain (the DNA-gate). Upon binding CTP, the N-terminal domain (NTD) self-dimerizes to close the NTD-gate of the clamp. The DNA-gate also closes, thus driving parS into a compartment between the DNA-gate and the C-terminal domain. CTP hydrolysis and/or the release of hydrolytic products are likely associated with reopening of the gates to release DNA and recycle ParB. Overall, we suggest a CTP-operated gating mechanism that regulates ParB nucleation, spreading, and recycling.

Journal Keywords: Research Advance; Chromosomes and Gene Expression; Caulobacter crescentus; chromosome segregation; spreading; molecular gates; ParA ParB parS; CTP

Diamond Keywords: Bacteria

Subject Areas: Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength)

Added On: 01/09/2021 09:02


Discipline Tags:

Genetics Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)