December 2017 - January 2018
Shen Wang, Yong Li, Chao Jiang, Haishan Tian
ABSTRACT - The fibroblast growth factor (FGF) 9 subfamily is a member of the FGF family, including FGF9, 16, and 20, potentially sharing similar biochemical functions due to their high degree of sequence homology. Unlike other secreted proteins which have a cleavable N-terminal secreted signal peptide, FGF9/16/20 have non-cleaved N-terminal signal peptides.
Thomas, JMH; Simkovic, F; Keegan, R; Mayans, O; Zhang, CX; Zhang, Y; Rigden, DJ
ABSTRACT - alpha-Helical transmembrane proteins are a ubiquitous and important class of proteins, but present difficulties for crystallographic structure solution. Here, the effectiveness of the AMPLE molecular replacement pipeline in solving alpha-helical transmembrane-protein structures is assessed using a small library of eight ideal helices, as well as search models derived from ab initio models generated both with and without evolutionary contact information
Leah J. Wilson, Adam Linley, Dean E. Hammond, Fiona E. Hood, Judy M. Coulson, David J. MacEwan, Sarah J. Ross, Joseph R. Slupsky, Paul D. Smith, Patrick A. Eyers and Ian A. Prior
ABSTRACT - The human protein kinome comprises 535 proteins that, with the exception of approximately 50 pseudokinases, control intracellular signaling networks by catalyzing the phosphorylation of multiple protein substrates
N. Kareema, E. Yates, M. Skidmore, D. Hoole
ABSTRACT - The rapid emergence of drug resistance, unfavourable immunosuppression and mounting evidence to suggest the deleterious accumulation of drug breakdown residues within animal tissues has driven a strong desire to move away from these current methods of disease control.
Rasha Swadi, Grace Mather, Barry L. Pizer, Paul D. Losty, Violaine See and Diana Moss
ABSTRACT - Neuroblastoma is a paediatric cancer that despite multimodal therapy still has a poor outcome for many patients with high risk tumours
Patrick A. Eyers
ABSTRACT - The addition of phosphate groups to substrates allows protein kinases to regulate a myriad of biological processes, and contextual analysis of protein-bound phosphate is important for understanding how kinases contribute to physiology and disease
Claire E Eyers, Matthias Vonderach, Samantha Ferries, Kiani Jeacock, Patrick A Eyers
ABSTRACT - Ion mobility–mass spectrometry (IM–MS) is an important addition to the analytical toolbox for the structural evaluation of proteins, and is enhancing many areas of biophysical analysis.
November 2017 - December 2017
Maura Rojas-Pirelaa, Daniel J. Rigden, Paul A. Michels, Ana J. Cáceres, Wilfredo Quiñones
ABTRACT - Per-ARNT-Sim (PAS) domains of proteins play important roles as modules for signalling and cellular regulation processes in widely diverse organisms such as Archaea, Bacteria, protists, plants, yeasts, insects and vertebrates. These domains are present in many proteins where they are used as sensors of stimuli and modules for protein interactions.
Phelan, M. M.; Caamano-Gutierrez, E.; Gant, M. S.; Grosman, R. X.; Madine, J.
ABSTRACT - The pathogenicity at differing points along the aggregation pathway of many fibril-forming proteins associated with neurodegenerative diseases is unclear. Understanding the effect of different aggregation states of these proteins on cellular processes is essential to enhance understanding of diseases and provide future options for diagnosis and therapeutic intervention.
Nina Karamanova, Seth Truran, Jillian Madine, Hannah Davies, Jenna Anderson, Daniel A Franco, Geidy Serrano, Thomas Beach, Raymond Q Migrino
ABSTRACT - Medin is the most common human amyloid protein and accumulates in vessels with aging yet little is known about the pathophysiology of medin and its role in vascular aging. We previously showed that medin, β-amyloid (Aβ42) and saturated fatty acid palmitic acid (PA) induce profound endothelial dysfunction in ex-vivo human adipose and leptomeningeal arterioles, suggesting potential interactions that could provide the missing link between cardiovascular risk factors (CVRFs) and amyloid proteins in inducing vascular dysfunction leading to atherosclerosis and cognitive dysfunction.
Seth Truran, Nina Karamanova, Jillian Madine, Hannah Davies, Diana Guzman-Villanueva, Geidy Serrano, Daniel A Franco, Thomas Beach, Volkmar Weissig, Raymond Q Migrino
ABSTRACT - Medin is a 50 amino acid peptide that forms amyloid deposits in the vasculature. It is the most common human amyloid protein and was reported to be present in almost all tested patients above 55 years old. It has been implicated as a potential novel etiologic risk factor for vascular aging yet we know little about its pathophysiology or treatment.
T. B. Almeida, A. J. Carnell, I. L. Barsukov, N.G. Berry
ABSTRACT - End binding protein 1 (EB1) is a key element in the complex network of protein-protein interactions at microtubule (MT) growing ends, which has a fundamental role in MT polymerisation. EB1 is an important protein target as it is involved in regulating MT dynamic behaviour, and has been associated with several disease states, such as cancer and neuronal diseases.
Thomas P. Halsted, Keitaro Yamashita, Kunio Hirata, Hideo Ago, Go Ueno, Takehiko Tosha Robert R. Eady Svetlana V. Antonyuk Masaki Yamamoto and S. Samar Hasnain
ABSTRACT - Synchrotron-based X-ray structural studies of ligand-bound enzymes are powerful tools to further our understanding of reaction mechanisms. For redox enzymes, it is necessary to study both the oxidized and reduced active sites to fully elucidate the reaction, an objective that is complicated by potential X-ray photoreduction. In the presence of the substrate, this can be exploited to construct a structural movie of the events associated with catalysis.
J. M. H. Thomas, F. Simkovic, R. Keegan, O. Mayans, C. Zhang, Y. Zhang and D. J. Rigden
ABSTRACT - Transmembrane proteins are an important class of proteins that are estimated to comprise about 30% of the proteome (Tusnády et al., 2004) They reside t least partly and often predominantly, within the hydrophobic cell membrane, sandwiched between the aqueous cell interior and exterior
Omid Mashinchian, Addolorata Pisconti, Emmeran Le Moal§, C. Florian Bentzinger
ABSTRACT - The regulation of stem cells that maintain and regenerate postnatal tissues depends on extrinsic signals originating from their microenvironment, commonly referred to as the stem cell niche.
October 2017 - November 2017
Maniaci C1,2, Hughes SJ1, Testa A1, Chen W1, Lamont DJ1, Rocha S3, Alessi DR2, Romeo R4, Ciulli A5
ABTRACT - E3 ubiquitin ligases are key enzymes within the ubiquitin proteasome system which catalyze the ubiquitination of proteins, targeting them for proteasomal degradation. E3 ligases are gaining importance as targets to small molecules, both for direct inhibition and to be hijacked to induce the degradation of non-native neo-substrates using bivalent compounds known as PROTACs (for 'proteolysis-targeting chimeras'). We describe Homo-PROTACs as an approach to dimerize an E3 ligase to trigger its suicide-type chemical knockdown inside cells
Nobuaki Takemori1, Ayako Takemori1, Yuki Tanaka2, Yaeta Endo1, Jane L. Hurst3, Guadalupe Gómez- Baena4, Victoria M Harman4 and Robert J Beynon4
ABSTRACT - A major challenge in proteomics is the absolute accurate quantification of large numbers of proteins. QconCATs, artificial proteins that are concatenations of multiple standard peptides, are well established as an efficient means to generate standards for proteome quantification
M. M. Phelan, E. Caamaño-Gutiérrez, M. S. Gant, R. X. Grosman, J. Madine
ABSTRACT - The pathogenicity at differing points along the aggregation pathway of many fibril-forming proteins associated with neurodegenerative diseases is unclear. Understanding the effect of different aggregation states of these proteins on cellular processes is essential to enhance understanding of diseases and provide future options for diagnosis and therapeutic intervention
Boyle, MJ; Skidmore, M; Dickerman, B; Cooper, L; Devlin, A ; Yates, E; Horrocks, P; Freeman, C; Chai, WG; Beeson, JG.
ABSTRACT - Despite recent successful control efforts, malaria remains a leading global health burden. Alarmingly, resistance to current antimalarials is increasing and the development of new drug families is needed to maintain malaria control. Current antimalarials target the intraerythrocytic developmental stage of the Plasmodium falciparum life cycle. However, the invasive extracellular parasite form, the merozoite, is also an attractive target for drug development
September 2017 - October 2017
Fiona P Bailey, Kim Clarke, Helen Kalirai, Jenna Kenyani, Haleh Shahidipour, Francesco Falciani, Judy M Coulson, Joseph J Sacco, Sarah E Coupland, Patrick A Eyers
ABSTRACT - Metastatic uveal melanoma (UM) is invariably fatal, usually within a year of diagnosis. There are currently no effective therapies, and clinical studies employing kinase inhibitors have so far demonstrated limited success.
Sally C. Dickenson, Catherine A. Sutton, Kyla Brady, Anna Salerno, Theoni Ktopodi, Rhys L. Williams, Christopher C. West, Denis Evseenko, Ling Wu, Suzanna Pang, Roberto Ferro de Godoy, Allen E. Goodship, Bruno PE Ault, Ashley W Blom, Wael Kafienah, Anthony P. Hollander
ABSTRACT - Multipotent mesenchymal stem cells (MSCs) have enormous potential in tissue engineering and regenerative medicine. However, until now their development for clinical use has been severely limited as they are a mixed population of cells with varying capacities for lineage differentiation and tissue formation
Gemma Hardman, Simon Perkins, Zheng Ruan, Natarajan Kannan, Philip Brownridge, Dominic P Byrne, Patrick A Eyers, Andrew R Jones, Claire E Eyers
ABSTRACT - Protein phosphorylation is a ubiquitous post-translational modification (PTM) that regulates all aspects of life. To date, investigation of human cell signalling has focussed on canonical phosphorylation of serine (Ser), threonine (Thr) and tyrosine (Tyr) residues. However, mounting evidence suggests that phosphorylation of histidine also plays a central role in regulating cell biology
Shen Wang, Haipeng Lin, Tiantian Zhao, Sisi Huang, David G. Fernig, Nuo Xu, Fenfang Wu, Mi Zhou, Chao Jiang, Haishan Tian
ABSTRACT - Fibroblast growth factor (FGF) 9 has oncogenic activity and plays an important role in the development of ovarian, lung, prostate, and gastric cancers
ABSTRACT - Despite recent successful control efforts, malaria remains a leading global health burden. Alarmingly, resistance to current antimalarials is increasing, and the development of new drug families is needed to maintain malaria control.
Local protein kinase A action proceeds through intact holoenzymes
Smith, F.D., Esseltine, J.L., Nygren, P.J., Veesler, D., Byrne, D.P., Vonderach, M., Strashnov, I., Eyers, C.E., Eyers, P.A., Langeberg, L.K., Scott, J.D. (2017) Local protein kinase A action proceeds through intact holoenzymes. Science. doi: 10.1126/science.aaj1669
Dynamic changes in heparan sulfate during muscle differentiation and ageing regulate myoblast cell fate and FGF2 signalling
Ghadiali, R.S., Guimond, S.E., Turnbull, J.E., Pisconti, A. (2017). Dynamic changes in heparan sulfate during muscle differentiation and ageing regulate myoblast cell fate and FGF2 signalling. Matrix Biology. doi: 10.1016/j.matbio.2016.07.007
MRL proteins cooperate with activated Ras in glia to drive distinct oncogenic outcomes
Taylor, E., Alqadri, N., Dodgson, L., Mason, D., Lyulcheva, E., Messina, G., Bennett, D. (2017). MRL proteins cooperate with activated Ras in glia to drive distinct oncogenic outcomes. Oncogene. doi: 10.1038/onc.2017.68
SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras
Lilja, J., Zacharchenko, T., Georgiadou, M., Jacquemet, G., Franceschi, N.D., Peuhu, E., Hamidi, H., Pouwels, J., Martens, V., Nia, F.H., Beifuss, M., Boeckers, T., Kreienkamp, H.-J., Barsukov, I.L., Ivaska, J. (2017). SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras. Nature Cell Biology. doi: 10.1038/ncb3487