ORCID Profile
0000-0002-3302-6966
Current Organisation
University of York
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: American Chemical Society (ACS)
Date: 08-11-2016
Publisher: Cold Spring Harbor Laboratory
Date: 24-12-2020
DOI: 10.1101/2020.12.24.424174
Abstract: Changes at the cell surface enable bacteria to survive in dynamic environments, such as erse niches of the human host. Here, we reveal “Periscope Proteins” as a widespread mechanism of bacterial surface alteration mediated through protein length variation. Tandem arrays of highly similar folded domains can form an elongated rod-like structure thus variation in the number of domains determines how far an N-terminal host ligand binding domain projects from the cell surface. Supported by newly-available long-read genome sequencing data, we propose this new class could contain over 50 distinct proteins, including those implicated in host colonisation and biofilm formation by human pathogens. In large multi-domain proteins, sequence ergence between adjacent domains appears to reduce inter-domain misfolding. Periscope Proteins break this “rule”, suggesting their length variability plays an important role in regulating bacterial interactions with host surfaces, other bacteria and the immune system.
Publisher: International Union of Crystallography (IUCr)
Date: 30-06-2015
DOI: 10.1107/S1399004715009220
Abstract: The reduction of uridine to dihydrouridine at specific positions in tRNA is catalysed by dihydrouridine synthase (Dus) enzymes. Increased expression of human dihydrouridine synthase 2 (hDus2) has been linked to pulmonary carcinogenesis, while its knockdown decreased cancer cell line viability, suggesting that it may serve as a valuable target for therapeutic intervention. Here, the X-ray crystal structure of a construct of hDus2 encompassing the catalytic and tRNA-recognition domains (residues 1–340) determined at 1.9 Å resolution is presented. It is shown that the structure can be determined automatically by phenix.mr_rosetta starting from a bacterial Dus enzyme with only 18% sequence identity and a significantly ergent structure. The overall fold of the human Dus2 is similar to that of bacterial enzymes, but has a larger recognition domain and a unique three-stranded antiparallel β-sheet insertion into the catalytic domain that packs next to the recognition domain, contributing to domain–domain interactions. The structure may inform the development of novel therapeutic approaches in the fight against lung cancer.
Publisher: Proceedings of the National Academy of Sciences
Date: 22-04-2015
Abstract: RNA-binding proteins use erse mechanisms for generating specificity toward distinct RNA molecules. Different subfamilies of bacterial dihydrouridine synthases (Dus) modify specific uridines in tRNA, but the mechanism for selection of the target nucleotide is unknown. We solved crystal structures of the U16-specific Dus from Escherichia coli complexed with two different tRNAs. These structures reveal that the tRNA is bound in a completely different orientation from that observed in a U20-specific enzyme. The major reorientation of the substrate tRNA, driven by unique amino acid “binding signatures” and plasticity in the position of the C-terminal recognition domain, appears to be an evolutionary innovation to the known strategies that define specificity of enzymes toward tRNA.
Publisher: Oxford University Press (OUP)
Date: 15-12-2015
DOI: 10.1093/NAR/GKV1467
Publisher: Proceedings of the National Academy of Sciences
Date: 31-05-2021
Abstract: The structure of single and tandem SHIRT domains from the streptococcal surface protein Sgo_0707 were determined. In conjunction with biophysics and molecular dynamics simulations, the results show that the observed gene length variation would result in differential projection of the host ligand binding domain on the bacterial cell surface. An analysis of long-read DNA sequence data reveals many other repetitive bacterial surface proteins that appear to undergo gene length variation. We propose that these variable-length “Periscope Proteins” represent an important mechanism of bacterial cell surface modification with potential roles in infection and immune evasion.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Huw Jenkins.