Identification and characterization of a G-quadruplex structure in the pre-core promoter region of hepatitis B virus covalently closed circular DNA

Meier-Stephenson, Vanessa; Badmalia, Maulik D.; Mrozowich, Tyler; Lau, Keith C.K.; Schultz, Sarah K.; Gemmill, Darren L.; Osiowy, Carla; Coffin, Carla S.; Patel, Trushar R.

doi:10.1016/j.jbc.2021.100589

Cited by 22 publications

(40 citation statements)

References 95 publications

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“…Using a Shodex KW402.5-4F column equilibrated in 20 mM Tris-HCl pH 7.5, 100 mM NaCl, 1 mM β-Me at the flow rate of 0.160 ml/min. Each frame was exposed to the X-rays for 3 s, as described previously ( 45 ). Data processing and analysis were first performed using the ATSAS ( 46 ) software package, including CHROMIXS ( 29 ) for peak selection and buffer subtraction and PRIMUS ( 30 ) for further data processing, including Guinier analysis and Kratky analysis.…”

Section: Methodsmentioning

confidence: 99%

Molecular mechanism of quorum sensing inhibition in Streptococcus by the phage protein paratox

Rutbeek

Rezasoltani

Patel

et al. 2021

Journal of Biological Chemistry

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Methodsmentioning

confidence: 99%

Molecular mechanism of quorum sensing inhibition in Streptococcus by the phage protein paratox

Rutbeek

Rezasoltani

Patel

et al. 2021

Journal of Biological Chemistry

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“…Using a Shodex KW402.5-4F column equilibrated in 20 mM Tris-HCl pH 7.5, 100 mM NaCl, 1 mM β-Me at the flow rate of 0.160 mL/min. Each frame was exposed to the X-rays for 3 seconds, as described previously (45). Data processing and analysis was first performed using the ATSAS (46) software package, including CHROMIXS (29) for peak selection and buffer subtraction, and PRIMUS (30) for further data processing, including Guinier analysis and Kratky analysis.…”

Section: Methodsmentioning

confidence: 99%

Molecular mechanism of quorum sensing inhibition in Streptococcus by the phage protein paratox

Rutbeek

Rezasoltani

Patel

et al. 2021

Preprint

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Streptococcus pyogenes, or Group A Streptococcus, is a Gram-positive bacterium that can be both a human commensal and pathogen. Central to this dichotomy are temperate bacteriophages that incorporate into the bacterial genome as a prophage. These genetic elements encode both the phage proteins as well as toxins harmful to the human host. One such conserved phage protein paratox (Prx) is always found encoded adjacent to the toxin genes and this linkage is preserved during transduction. Within Streptococcus pyogenes, Prx functions to inhibit the quorum-sensing ComRS receptor-signal pair that is the master regulator of natural competence, or the ability to uptake endogenous DNA. Specifically, Prx directly binds and inhibits the receptor ComR by unknown mechanism. To understand how Prx inhibits ComR at the molecular level we pursued an X-ray crystal structure of Prx bound to ComR. The structural data supported by solution X-ray scattering data demonstrate that Prx induces a conformational change in ComR to directly access the DNA binding domain. Furthermore, electromobility shift assays and competition binding assays reveal that Prx effectively uncouples the inter-domain conformational change that is required for activation of ComR by the signaling molecule XIP. Although to our knowledge the molecular mechanism of quorum-sensing inhibition by Prx is unique, it is analogous to the mechanism employed by the phage protein Aqs1 in Pseudomonas aeruginosa. Together, this demonstrates an example of convergent evolution between Gram-positive and Gram-negative phages to inhibit quorum-sensing, and highlights the versatility of small phage proteins.

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“…In the C-MYC promoter, a G4Q represses transcription and can be unwound by the MAZ protein to derepress it (Siddiqui-Jain et al 2002a ). Similarly, in the HRAS promoter, there are two upstream quadruplexes that maintain transcriptional repression, which when bound and unwound by MAZ are able to proceed with their downstream processing (Cogoi et al 2014 ; Membrino et al 2011 ). MAZ can also bind and unwind the Pur-1 G4Q of the IDDM2 locus to enable transcription (Lew et al 2000 ).…”

Section: G4bps Targeting Promotersmentioning

confidence: 99%

“…It is beyond the scope of this review, but it may be interesting to review the details of prior such zinc finger interaction studies to determine whether the experimental conditions of each would have supported the formation of G4Qs and thus have the potential to infer results on these structures. Of the promoter regions Sp1 is known to interact and regulate, those containing G4Qs at the site of Sp1 binding are c-KIT (Da Ros et al 2021 ), HRAS (Cogoi et al 2014 ; Membrino et al 2011 ), and VEGF (Yokono et al 1998 ). In the case of HRAS, Sp1 binding to its G4Q promoter acts as a transcriptional repressor and seems to also require MAZ (another G4Q-binding zinc finger protein, noted above) for its action (Membrino et al 2011 ).…”

Section: G4bps Targeting Promotersmentioning

confidence: 99%

G4-quadruplex-binding proteins: review and insights into selectivity

Meier-Stephenson

2022

Biophys Rev

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There are over 700,000 putative G4-quadruplexes (G4Qs) in the human genome, found largely in promoter regions, telomeres, and other regions of high regulation. Growing evidence links their presence to functionality in various cellular processes, where cellular proteins interact with them, either stabilizing and/or anchoring upon them, or unwinding them to allow a process to proceed. Interest in understanding and manipulating the plethora of processes regulated by these G4Qs has spawned a new area of small-molecule binder development, with attempts to mimic and block the associated G4-binding protein (G4BP). Despite the growing interest and focus on these G4Qs, there is limited data (in particular, high-resolution structural information), on the nature of these G4Q-G4BP interactions and what makes a G4BP selective to certain G4Qs, if in fact they are at all. This review summarizes the current literature on G4BPs with regards to their interactions with G4Qs, providing groupings for binding mode, drawing conclusions around commonalities and highlighting information on specific interactions where available.

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Identification and characterization of a G-quadruplex structure in the pre-core promoter region of hepatitis B virus covalently closed circular DNA

Cited by 22 publications

References 95 publications

Molecular mechanism of quorum sensing inhibition in Streptococcus by the phage protein paratox

Molecular mechanism of quorum sensing inhibition in Streptococcus by the phage protein paratox

Molecular mechanism of quorum sensing inhibition in Streptococcus by the phage protein paratox

G4-quadruplex-binding proteins: review and insights into selectivity

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