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All Outputs (14)

Factor XII and kininogen asymmetric assembly with gC1qR/C1QBP/P32 is governed by allostery (2020)
Journal Article
Kaira, B. G., Slater, A., McCrae, K. R., Dreveny, I., Sumya, U., Mutch, N. J., …Emsley, J. (2020). Factor XII and kininogen asymmetric assembly with gC1qR/C1QBP/P32 is governed by allostery. Blood, 136(14), 1685–1697. https://doi.org/10.1182/blood.2020004818

The contact system is composed of Factor XII (FXII), prekallikrein (PK) and co-factor kininogen (HK). The globular C1q receptor (gC1qR) has been shown to interact with FXII and HK. We reveal the FXII fibronectin type II domain (FnII) binds gC1qR in a... Read More about Factor XII and kininogen asymmetric assembly with gC1qR/C1QBP/P32 is governed by allostery.

Structural basis of the leukocyte integrin Mac-1 I-domain interactions with the platelet glycoprotein Ib (2019)
Journal Article
Morgan, J., Saleem, M., Ng, R., Armstrong, C., Wong, S. S., Caulton, S. G., …Emsley, J. (2019). Structural basis of the leukocyte integrin Mac-1 I-domain interactions with the platelet glycoprotein Ib. Blood Advances, 3(9), 1450-1459. https://doi.org/10.1182/bloodadvances.2018027011

Cell-surface receptor interactions between leukocyte integrin macrophage-1 antigen (Mac-1, also known as CR3, aMb2, CD11b/CD18) and platelet glycoprotein Iba (GPIba) are critical to vascular inflammation. To define the key residues at the binding inter... Read More about Structural basis of the leukocyte integrin Mac-1 I-domain interactions with the platelet glycoprotein Ib.

DNA replication initiation in Bacillus subtilis: Structural and functional characterization of the essential DnaA-DnaD interaction (2018)
Journal Article
Martin, E., Williams, H. E., Pitoulias, M., Stevens, D., Winterhalter, C., Craggs, T. D., …Soultanas, P. (2019). DNA replication initiation in Bacillus subtilis: Structural and functional characterization of the essential DnaA-DnaD interaction. Nucleic Acids Research, 47(4), 2101-2112. https://doi.org/10.1093/nar/gky1220

© 2018 The Author(s). The homotetrameric DnaD protein is essential in low G+C content gram positive bacteria and is involved in replication initiation at oriC and re-start of collapsed replication forks. It interacts with the ubiquitously conserved b... Read More about DNA replication initiation in Bacillus subtilis: Structural and functional characterization of the essential DnaA-DnaD interaction.

ALS-FTLD associated mutations of SQSTM1 impact on Keap1-Nrf2 signalling (2016)
Journal Article
Goode, A., Rea, S., Sultana, M., Shaw, B., Searle, M. S., & Layfield, R. (2016). ALS-FTLD associated mutations of SQSTM1 impact on Keap1-Nrf2 signalling. Molecular and Cellular Neuroscience, 76, https://doi.org/10.1016/j.mcn.2016.08.004

The transcription factor Nrf2 and its repressor protein Keap1 play key roles in the regulation of antioxidant stress responses and both Keap1-Nrf2 signalling and oxidative stress have been implicated in the pathogenesis of the ALS-FTLD spectrum of ne... Read More about ALS-FTLD associated mutations of SQSTM1 impact on Keap1-Nrf2 signalling.

Mass spectrometry insights into a tandem ubiquitin-binding domain hybrid engineered for the selective recognition of unanchored polyubiquitin (2016)
Journal Article
Scott, D., Garner, T. P., Long, J., Strachan, J., Mistry, S. C., Bottrill, A. R., …Layfield, R. (in press). Mass spectrometry insights into a tandem ubiquitin-binding domain hybrid engineered for the selective recognition of unanchored polyubiquitin. Proteomics, 16(14), https://doi.org/10.1002/pmic.201600067

Unanchored polyubiquitin chains are emerging as importanregulators of cellular physiology with diverse roles paralleling those of substrate-conjugated polyubiquitin. However tools able to discriminate unanchored polyubiquitin chains of different isop... Read More about Mass spectrometry insights into a tandem ubiquitin-binding domain hybrid engineered for the selective recognition of unanchored polyubiquitin.

Defective recognition of LC3B by mutant SQSTM1/p62 implicates impairment of autophagy as a pathogenic mechanism in ALS-FTLD (2016)
Journal Article
Goode, A., Butler, K., Long, J., Cavey, J., Scott, D., Shaw, B., …Layfield, R. (2016). Defective recognition of LC3B by mutant SQSTM1/p62 implicates impairment of autophagy as a pathogenic mechanism in ALS-FTLD. Autophagy, 12(7), 1094-1104. https://doi.org/10.1080/15548627.2016.1170257

Growing evidence implicates impairment of autophagy as a candidate pathogenic mechanism in the spectrum of neurodegenerative disorders which includes amyotrophic lateral sclerosis and frontotemporal lobar degeneration (ALS-FTLD). SQSTM1, which encode... Read More about Defective recognition of LC3B by mutant SQSTM1/p62 implicates impairment of autophagy as a pathogenic mechanism in ALS-FTLD.

SilE is an intrinsically disordered periplasmic ‘molecular sponge' involved in bacterial silver resistance (2016)
Journal Article
Asiani, K. R., Williams, H. E. L., Bird, L., Jenner, M., Searle, M. S., Hobman, J. L., …Soultanas, P. (2016). SilE is an intrinsically disordered periplasmic ‘molecular sponge' involved in bacterial silver resistance. Molecular Microbiology, 101(5), 731-742. https://doi.org/10.1111/mmi.13399

Ag+ resistance was initially found on the Salmonella enetrica serovar Typhimurium multi-resistance plasmid pMG101 from burns patients in 1975. The putative model of Ag+ resistance, encoded by the sil operon from pMG101, involves export of Ag+ via an... Read More about SilE is an intrinsically disordered periplasmic ‘molecular sponge' involved in bacterial silver resistance.

Enantiopure titanocene complexes: direct evidence for paraptosis in cancer cells (2016)
Journal Article
Cini, M., Williams, H. E. L., Fay, M. W., Searle, M., Woodward, S., & Bradshaw, T. D. (2016). Enantiopure titanocene complexes: direct evidence for paraptosis in cancer cells. Metallomics, https://doi.org/10.1039/C5MT00297D

Tolerated by normal tissues, anti-cancer therapies based on titanium compounds are limited by low efficacy/selectivity and lack of understanding of their mode(s) of action. In vitro antitumour activity and mode of cell death incurred by enantiopure T... Read More about Enantiopure titanocene complexes: direct evidence for paraptosis in cancer cells.

Ligand selectivity in stabilising tandem parallel folded G-quadruplex motifs in human telomeric DNA sequences (2014)
Journal Article
Cousins, A. R., Searle, M. S., Ritson, D., Sharma, P., Stevens, M. F., & Moses, J. E. (2014). Ligand selectivity in stabilising tandem parallel folded G-quadruplex motifs in human telomeric DNA sequences. Chemical Communications, 50(96), 15202-15205. https://doi.org/10.1039/c4cc07487d

© The Royal Society of Chemistry 2014. Biophysical studies of ligand interactions with three human telomeric repeat sequences (d(AGGG(TTAGGG)n, n = 3, 7 and 11)) show that an oxazole-based 'click' ligand, which induces parallel folded quadruplexes, p... Read More about Ligand selectivity in stabilising tandem parallel folded G-quadruplex motifs in human telomeric DNA sequences.

A Targeted Oligonucleotide Enhancer of SMN2 Exon 7 Splicing Forms Competing Quadruplex and Protein Complexes in Functional Conditions (2014)
Journal Article
Smith, L., Dickinson, R., Lucas, C., Cousins, A., Malygin, A., Weldon, C., …Eperon, I. (2014). A Targeted Oligonucleotide Enhancer of SMN2 Exon 7 Splicing Forms Competing Quadruplex and Protein Complexes in Functional Conditions. Cell Reports, 9(1), 193-205. https://doi.org/10.1016/j.celrep.2014.08.051

The use of oligonucleotides to activate the splicing of selected exons is limited by a poor understanding of the mechanisms affected. A targeted bifunctional oligonucleotide enhancer of splicing (TOES) anneals to SMN2 exon 7 and carries an exonic spl... Read More about A Targeted Oligonucleotide Enhancer of SMN2 Exon 7 Splicing Forms Competing Quadruplex and Protein Complexes in Functional Conditions.

A sequence-based approach for prediction of CsrA/RsmA targets in bacteria with experimental validation in Pseudomonas aeruginosa (2014)
Journal Article
Kulkarni, P. R., Jia, T., Kuehne, S. H., Kerkering, T. M., Morris, E. R., Searle, M. S., …Kulkarni, R. V. (in press). A sequence-based approach for prediction of CsrA/RsmA targets in bacteria with experimental validation in Pseudomonas aeruginosa. Nucleic Acids Research, 42(11), https://doi.org/10.1093/nar/gku309

CsrA/RsmA homologs are an extensive family of ribonucleic acid (RNA)-binding proteins that function as global post-transcriptional regulators controlling important cellular processes such as secondary metabolism, motility, biofilm formation and the p... Read More about A sequence-based approach for prediction of CsrA/RsmA targets in bacteria with experimental validation in Pseudomonas aeruginosa.

Paget disease of bone-associated UBA domain mutations of SQSTM1 exert distinct effects on protein structure and function (2014)
Journal Article
Goode, A., Long, J. E., Shaw, B., Ralston, S. H., Visconti, M. R., Gianfrancesco, F., …Layfield, R. (2014). Paget disease of bone-associated UBA domain mutations of SQSTM1 exert distinct effects on protein structure and function. BBA - Molecular Basis of Disease, 1842(7), 992-1000. https://doi.org/10.1016/j.bbadis.2014.03.006

SQSTM1 mutations are common in patients with Paget disease of bone (PDB), with most affecting the C-terminal ubiquitin-associated (UBA) domain of the SQSTM1 protein. We performed structural and functional analyses of two UBA domain mutations, an I424... Read More about Paget disease of bone-associated UBA domain mutations of SQSTM1 exert distinct effects on protein structure and function.