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Your search keyword '"Bycroft, Mark"' showing total 16 results
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16 results on '"Bycroft, Mark"'

8. Recruitment ofTBK1 to cytosol‐invadingSalmonellainducesWIPI2‐dependent antibacterial autophagy

Author

Thurston, Teresa LM, primary, Boyle, Keith B, additional, Allen, Mark, additional, Ravenhill, Benjamin J, additional, Karpiyevich, Maryia, additional, Bloor, Stuart, additional, Kaul, Annie, additional, Noad, Jessica, additional, Foeglein, Agnes, additional, Matthews, Sophie A, additional, Komander, David, additional, Bycroft, Mark, additional, and Randow, Felix, additional

Published
2016
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10. The structure of INI1/hSNF5 RPT1 and its interactions with the c‐MYC:MAX heterodimer provide insights into the interplay between MYC and the SWI/SNF chromatin remodeling complex.

Author

Sammak, Susan, Allen, Mark D., Hamdani, Najoua, Bycroft, Mark, and Zinzalla, Giovanna

Subjects
HETERODIMERS, CHROMATIN, GENETIC transcription, MOLECULAR structure, PROTEIN-protein interactions
Abstract

c‐MYC and the SWI/SNF chromatin remodeling complex act as master regulators of transcription, and play a key role in human cancer. Although they are known to interact, the molecular details of their interaction are lacking. We have determined the structure of the RPT1 region of the INI1/hSNF5/BAF47/SMARCB1 subunit of the SWI/SNF complex that acts as a c‐MYC‐binding domain, and have localized the interaction regions on both INI1 and on the c‐MYC:MAX heterodimer. c‐MYC interacts with a highly conserved groove on INI1, while INI1 binds to the c‐MYC helix‐loop‐helix region. The binding site overlaps with the c‐MYC DNA‐binding region, and we show that binding of INI1 and E‐box DNA to c‐MYC:MAX are mutually exclusive. c‐MYC interacts with the INI1/hSNF5/BAF47/SMARCB1 subunit of the SWI/SNF chromatin remodeling complex. We have determined the structure of INI1 RPT1 that acts as a c‐MYC‐binding domain, and localized the interaction regions on both INI1 and the c‐MYC:MAX heterodimer. The binding site overlaps with the c‐MYC DNA‐binding region. We show that binding of INI1 and E‐box DNA to c‐MYC:MAX are mutually exclusive. [ABSTRACT FROM AUTHOR]

Published
2018
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14. High-resolution NMR structures of the domains of Saccharomyces cerevisiae Tho1.

Author

Jacobsen, Julian O. B., Allen, Mark D., Freund, Stefan M. V., and Bycroft, Mark

Subjects
FUNGAL protein structure, NUCLEAR magnetic resonance spectroscopy, SACCHAROMYCES cerevisiae
Abstract

THO is a multi-protein complex involved in the formation of messenger ribonuclear particles (mRNPs) by coupling transcription with mRNA processing and export. THO is thought to be formed from five subunits, Tho2p, Hpr1p, Tex1p, Mft1p and Thp2p, and recent work has determined a low-resolution structure of the complex [Poulsen et al. (2014), PLoS One, 9, e103470]. A number of additional proteins are thought to be involved in the formation of mRNP in yeast, including Tho1, which has been shown to bind RNA in vitro and is recruited to actively transcribed chromatin in vivo in a THO-complex and RNA-dependent manner. Tho1 is known to contain a SAP domain at the N-terminus, but the ability to suppress the expression defects of the hpr1Δ mutant of THO was shown to reside in the RNA-binding C-terminal region. In this study, high-resolution structures of both the N-terminal DNA-binding SAP domain and C-terminal RNA-binding domain have been determined. [ABSTRACT FROM AUTHOR]

Published
2016
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16. SWI/SNF subunit BAF155 N-terminus structure informs the impact of cancer-associated mutations and reveals a potential drug binding site

Author

Mark D. Allen, Giovanna Zinzalla, Stefan M.V. Freund, Mark Bycroft, Bycroft, Mark [0000-0002-0673-2216], Zinzalla, Giovanna [0000-0002-1130-4865], and Apollo - University of Cambridge Repository

Subjects
Models, Molecular, Cancer therapy, QH301-705.5, Protein Conformation, Protein subunit, 631/67/1059, 101/6, Medicine (miscellaneous), General Biochemistry, Genetics and Molecular Biology, Chromodomain, 82/80, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Missense mutation, Humans, Binding site, Biology (General), 82/83, 030304 developmental biology, X-ray crystallography, 0303 health sciences, Binding Sites, Chemistry, article, Small molecule, SWI/SNF, Cell biology, BRCT domain, Pharmaceutical Preparations, 631/535/1266, 030220 oncology & carcinogenesis, Mutation, Drug Binding Site, General Agricultural and Biological Sciences, Transcription Factors
Abstract

SWI/SNF (BAF) chromatin remodelling complexes are key regulators of gene expression programs, and attractive drug targets for cancer therapies. Here we show that the N-terminus of the BAF155/SMARCC1 subunit contains a putative DNA-binding MarR-like domain, a chromodomain and a BRCT domain that are interconnected to each other to form a distinct module. In this structure the chromodomain makes interdomain interactions and has lost its canonical function to bind to methylated lysines. The structure provides new insights into the missense mutations that target this module in cancer. This study also reveals two adjacent, highly-conserved pockets in a cleft between the domains that form a potential binding site, which can be targeted with small molecules, offering a new strategy to target SWI/SNF complexes., Allen et al. determine crystal structure of the N-terminus of SWI/SNF chromatin remodelling factor subunit BAF155. They identify an interconnected structure of MarR-like, BRCT and chromodomains, visualise the potential effect of cancer-associated missense mutations and suggest a binding site and target for small molecule inhibitors.

Published
2021
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