Dr John Viles
Reader in Biochemistry
School of Biological and Behavioural Sciences
Queen Mary University of London
Queen Mary University of London
Research
Amyloids, Protein Misfolding, Alzheimer\'s, Prions, Bioinorganic Chemistry
Interests
Dr John H. Viles uses a range of biophysical techniques to study the fundamental processes that influence neurotoxic oligomer and amyloid plaque formation in Alzheimer’s, Parkinson’s and Prion disease. Approaches include biomolecular spectroscopies, NMR and CD, together with imaging techniques EM and AFM. With a focus on the kinetics of fibril formation, lipid-bilayer and metal integrations with amyloid forming proteins.Publications
Publications of specific relevance to the Centre for Molecular Cell Biology2024
Tian Y, Shang Q, Liang R and Viles JH (2024). Copper(II) Can Kinetically Trap Arctic and Italian Amyloid‑β40 as Toxic Oligomers, Mimicking Cu(II) Binding to Wild-Type Amyloid‑β42: Implications for Familial Alzheimer’s Disease. JACS Au, American Chemical Society (ACS) 06-02-2024
Khursheed A and Viles JH (2024). Impact of Membrane Phospholipids and Exosomes on the Kinetics of Amyloid-β Fibril Assembly. Journal of Molecular Biology, Elsevier vol. 436 (6) 03-02-2024
2023
Viles JH (2023). Imaging Amyloid‐β Membrane Interactions: Ion‐Channel Pores and Lipid‐Bilayer Permeability in Alzheimer's Disease. Angewandte Chemie, Wiley vol. 135 (25) 30-03-2023
2022
Tian Y and Viles JH (2022). pH Dependence of Amyloid-β Fibril Assembly Kinetics: Unravelling the Microscopic Molecular Processes. Angewandte Chemie International Edition, Wiley 05-10-2022
Tian Y and Viles JH (2022). pH Dependence of Amyloid‐β Fibril Assembly Kinetics: Unravelling the Microscopic Molecular Processes. Angewandte Chemie, Wiley 05-10-2022
Liang R, Tian Y and Viles JH (2022). Cross-seeding of WT amyloid-β with Arctic but not Italian familial mutants accelerates fibril formation in Alzheimer's disease. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology vol. 298 (7) 01-07-2022
Tian Y, Liu J, Yang F, Lian C, Zhang H, Viles JH and Li Z (2022). Therapeutic potential for amyloid surface inhibitor: only amyloid-β oligomers formed by secondary nucleation disrupt lipid membrane integrity. FEBS Journal 19-06-2022
2021
Tian Y, Liang R, Kumar A, Szwedziak P and Viles JH (2021). 3D-visualization of amyloid-β oligomer interactions with lipid membranes by cryo-electron tomography. Chemical Science, Royal Society of Chemistry (RSC) vol. 12 (20), 6896-6907. 01-01-2021
2019
Tian Y, Stanyon HF, Barritt JD, Mayet U, Patel P, Karamani E, Fusco G and Viles JH (2019). Copper2+ Binding to α-Synuclein. Histidine50 Can Form a Ternary Complex with Cu2+ at the N-Terminus but Not a Macrochelate. Inorganic Chemistry: including bioinorganic chemistry, American Chemical Society vol. 58 (22), 15580-15589. 07-11-2019
Bode DC, Freeley M, Nield J, Palma M and Viles JH (2019). Amyloid-β oligomers have a profound detergent-like effect on lipid membrane bilayers, imaged by atomic force and electron microscopy. J Biol Chem vol. 294 (19), 7566-7572. 10-05-2019
2018
VILES JH (2018). Copper Redox Cycling Inhibits Aβ Fibre Formation and Promotes Fibre Fragmentation, while Generating a Dityrosine Aβ Dimer. Scientific Reports, Nature Publishing Group 01-11-2018
Younan ND, Chen K-F, Rose R-S, Crowther DC and Viles JH (2018). Prion protein stabilizes amyloid-β (Aβ) oligomers and enhances Aβ neurotoxicity in a Drosophila model of Alzheimer's disease. J Biol Chem vol. 293 (34), 13090-13099. 24-08-2018
Bode DC, Stanyon HF, Hirani T, Baker MD, Nield J and Viles JH (2018). Serum Albumin's Protective Inhibition of Amyloid-β Fibre Formation Is Suppressed by Cholesterol, Fatty Acids and Warfarin. J Mol Biol 02-02-2018
2017
Barritt JD, Younan ND and Viles JH (2017). N-Terminally Truncated Amyloid-β(11-40/42) Cofibrillizes with its Full-Length Counterpart: Implications for Alzheimer's Disease. Angew Chem Int Ed Engl vol. 56 (33), 9816-9819. 07-08-2017
Barritt JD, Younan ND and Viles JH (2017). N‐Terminally Truncated Amyloid‐β(11–40/42) Cofibrillizes with its Full‐Length Counterpart: Implications for Alzheimer's Disease. Angewandte Chemie, Wiley vol. 129 (33), 9948-9951. 28-07-2017
2016
BAKER MD (2016). Ion Channel Formation by Amyloid-β42 Oligomers but not Amyloid-β40 in Cellular Membranes. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology 07-12-2016
Matheou CJ, Younan ND and Viles JH (2016). The Rapid Exchange of Zinc2+ Enables Trace Levels to Profoundly Influence Amyloid-β Misfolding and Dominates Assembly Outcomes in Cu2+/Zn2+ Mixtures. Journal of Molecular Biology vol. 428 (14), 2832-2846. 16-06-2016
Gu M and Viles JH (2016). Methionine oxidation reduces lag-times for Amyloid-β(1–40) fibre formation but generates highly fragmented fibres. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics 22-04-2016
Shahzad R, Jones MR, Viles JH and Jones CE (2016). Endocytosis of the tachykinin neuropeptide, neurokinin B, in astrocytes and its role in cellular copper uptake. Journal of Inorganic Biochemistry, Elsevier vol. 162, 319-325. 27-02-2016
2015
Barritt JD and Viles JH (2015). Truncated Amyloid-β(11–40/42) from Alzheimer Disease Binds Cu2+ with a Femtomolar Affinity and Influences Fiber Assembly*. Journal of Biological Chemistry, Elsevier vol. 290 (46), 27791-27802. 25-09-2015
Younan ND and Viles JH (2015). A Comparison of Three Fluorophores for the Detection of Amyloid Fibers and Prefibrillar Oligomeric Assemblies. ThT (Thioflavin T); ANS (1-Anilinonaphthalene-8-sulfonic Acid); and bisANS (4,4′-Dianilino-1,1′-binaphthyl-5,5′-disulfonic Acid). Biochemistry, American Chemical Society (ACS) vol. 54 (28), 4297-4306. 10-07-2015
Nasica-Labouze J, Nguyen PH, Sterpone F, Berthoumieu O, Buchete N-V, Coté S, De Simone A, Doig AJ, Faller P, Garcia A, Laio A, Li MS, Melchionna S, Mousseau N, Mu Y, Paravastu A, Pasquali S, Rosenman DJ, Strodel B, Tarus B, et al. (2015). Amyloid β Protein and Alzheimer’s Disease: When Computer Simulations Complement Experimental Studies. Chemical Reviews, American Chemical Society (ACS) vol. 115 (9), 3518-3563. 19-03-2015
Matheou CJ, Younan ND and Viles JH (2015). Cu²⁺ accentuates distinct misfolding of Aβ₁₋₄₀ and Aβ₁₋₄₂ peptides, and potentiates membrane disruption. Biochemical Journal, Portland Press vol. 466 (2), 233-242. 20-02-2015
2014
Jones CE, Otara CB, Younan ND, Viles JH and Elphick MR (2014). Bioactivity and structural properties of chimeric analogs of the starfish SALMFamide neuropeptides S1 and S2. Biochim Biophys Acta vol. 1844 (10), 1842-1850. 01-10-2014
Stanyon HF, Cong X, Chen Y, Shahidullah N, Rossetti G, Dreyer J, Papamokos G, Carloni P and Viles JH (2014). Developing predictive rules for coordination geometry from visible circular dichroism of copper(II) and nickel(II) ions in histidine and amide main-chain complexes. FEBS J vol. 281 (17), 3945-3954. 01-09-2014
Stanyon HF, Patel K, Begum N and Viles JH (2014). Copper(II) sequentially loads onto the N-terminal amino group of the cellular prion protein before the individual octarepeats. Biochemistry vol. 53 (24), 3934-3999. 24-06-2014
Otara CB, Jones CE, Younan ND, Viles JH and Elphick MR (2014). Structural analysis of the starfish SALMFamide neuropeptides S1 and S2: the N-terminal region of S2 facilitates self-association. Biochim Biophys Acta vol. 1844 (2), 358-365. 01-02-2014
2013
Younan ND, Sarell CJ, Davies P, Brown DR and Viles JH (2013). The cellular prion protein traps Alzheimer's Aβ in an oligomeric form and disassembles amyloid fibers. FASEB J vol. 27 (5), 1847-1858. 01-05-2013
2012
Younan ND, Nadal RC, Davies P, Brown DR and Viles JH (2012). Methionine oxidation perturbs the structural core of the prion protein and suggests a generic misfolding pathway. J Biol Chem vol. 287 (34), 28263-28275. 17-08-2012
Stanyon HF and Viles JH (2012). Human serum albumin can regulate amyloid-β peptide fiber growth in the brain interstitium: implications for Alzheimer disease. J Biol Chem vol. 287 (33), 28163-28168. 10-08-2012
Viles JH (2012). Metal ions and amyloid fiber formation in neurodegenerative diseases. Copper, zinc and iron in Alzheimer's, Parkinson's and prion diseases. COORDINATION CHEMISTRY REVIEWS vol. 256 (19-20), 2271-2284. 01-01-2012
2011
Younan ND, Klewpatinond M, Davies P, Ruban AV, Brown DR and Viles JH (2011). Copper(II)-induced secondary structure changes and reduced folding stability of the prion protein. J Mol Biol vol. 410 (3), 369-382. 15-07-2011
Davies P, Wang X, Sarell CJ, Drewett A, Marken F, Viles JH and Brown DR (2011). The synucleins are a family of redox-active copper binding proteins. Biochemistry vol. 50 (1), 37-47. 11-01-2011
2010
Sarell CJ, Wilkinson SR and Viles JH (2010). Substoichiometric levels of Cu2+ ions accelerate the kinetics of fiber formation and promote cell toxicity of amyloid-{beta} from Alzheimer disease. J Biol Chem vol. 285 (53), 41533-41540. 31-12-2010
Wright HM, Wyatt PB and Viles JH (2010). Is oxidation the trigger of the Amyloid Cascade?: A synthesis of 2-oxo-histidine for incorporation into the Amyloid beta sequence. J PEPT SCI vol. 16, 66-66. 01-09-2010
2009
Nadal RC, Davies P, Brown DR and Viles JH (2009). Evaluation of copper2+ affinities for the prion protein. Biochemistry vol. 48 (38), 8929-8931. 29-09-2009
Sarell CJ, Syme CD, Rigby SEJ and Viles JH (2009). Copper(II) binding to amyloid-beta fibrils of Alzheimer's disease reveals a picomolar affinity: stoichiometry and coordination geometry are independent of Abeta oligomeric form. Biochemistry vol. 48 (20), 4388-4402. 26-05-2009
O'Sullivan DBD, Jones CE, Abdelraheim SR, Brazier MW, Toms H, Brown DR and Viles JH (2009). Dynamics of a truncated prion protein, PrP(113-231), from (15)N NMR relaxation: order parameters calculated and slow conformational fluctuations localized to a distinct region. Protein Sci vol. 18 (2), 410-423. 01-02-2009
2008
Viles JH, Klewpatinond M and Nadal RC (2008). Copper and the structural biology of the prion protein. Biochem Soc Trans vol. 36 (Pt 6), 1288-1292. 01-12-2008
Nadal RC, Rigby SEJ and Viles JH (2008). Amyloid beta-Cu2+ complexes in both monomeric and fibrillar forms do not generate H2O2 catalytically but quench hydroxyl radicals. Biochemistry vol. 47 (44), 11653-11664. 04-11-2008
Brazier MW, Davies P, Player E, Marken F, Viles JH and Brown DR (2008). Manganese binding to the prion protein. J Biol Chem vol. 283 (19), 12831-12839. 09-05-2008
Klewpatinond M, Davies P, Bowen S, Brown DR and Viles JH (2008). Deconvoluting the Cu2+ binding modes of full-length prion protein. J BIOL CHEM vol. 283 (4), 1870-1881. 25-01-2008
2007
Klewpatinond M and Viles JH (2007). Fragment length influences affinity for Cu2+ and Ni2+ binding to His(96) or His(111) of the prion protein and spectroscopic evidence for a multiple histidine binding only at low pH. BIOCHEM J vol. 404, 393-402. 15-06-2007
Klewpatinond M and Viles JH (2007). Empirical rules for rationalising visible circular dichroism of Cu2+ and Ni2+ histidine complexes: Applications to the prion protein. FEBS LETT vol. 581 (7), 1430-1434. 03-04-2007
O'Sullivan DBD, Jones CE, Abdelraheim SR, Thompsett AR, Brazier MW, Toms H, Brown DR and Viles JH (2007). NMR characterization of the pH 4 beta-intermediate of the prion protein: the N-terminal half of the protein remains unstructured and retains a high degree of flexibility. Biochem J vol. 401 (2), 533-540. 15-01-2007
Nadal RC, Abdelraheim SR, Brazier MW, Rigby SEJ, Brown DR and Viles JH (2007). Prion protein does not redox-silence Cu2+, but is a sacrificial quencher of hydroxyl radicals. Free Radic Biol Med vol. 42 (1), 79-89. 01-01-2007
2006
Syme CD and Viles JH (2006). Solution 1H NMR investigation of Zn2+ and Cd2+ binding to amyloid-beta peptide (Abeta) of Alzheimer's disease. Biochim Biophys Acta vol. 1764 (2), 246-256. 01-02-2006
Garnett AP, Jones CE and Viles JH (2006). A survey of diamagnetic probes for copper2+ binding to the prion protein. 1H NMR solution structure of the palladium2+ bound single octarepeat. Dalton Trans (3), 509-518. 21-01-2006
2005
Viles JH (2005). Copper and the prion protein: Function and dysfunction. The Biochemist, Portland Press vol. 27 (4), 9-12. 01-08-2005
Otara CB, Jones CE, Melarange R, Viles JH and Elphick MR (2005). Tertiary structure and activity of SALMFamide neuropeptides. COMP BIOCHEM PHYS A vol. 141 (3), S161-S161. 01-07-2005
Jones CE, Klewpatinond M, Abdelraheim SR, Brown DR and Viles JH (2005). Probing copper2+ binding to the prion protein using diamagnetic nickel2+ and 1H NMR: the unstructured N terminus facilitates the coordination of six copper2+ ions at physiological concentrations. J Mol Biol vol. 346 (5), 1393-1407. 11-03-2005
2004
Jones CE, Abdelraheim SR, Brown DR and Viles JH (2004). Preferential Cu2+ coordination by His96 and His111 induces beta-sheet formation in the unstructured amyloidogenic region of the prion protein. J Biol Chem vol. 279 (31), 32018-32027. 30-07-2004
Syme CD, Nadal RC, Rigby SEJ and Viles JH (2004). Copper binding to the amyloid-beta (Abeta) peptide associated with Alzheimer's disease: folding, coordination geometry, pH dependence, stoichiometry, and affinity of Abeta-(1-28): insights from a range of complementary spectroscopic techniques. J Biol Chem vol. 279 (18), 18169-18177. 30-04-2004
2003
Garnett AP and Viles JH (2003). Copper binding to the octarepeats of the prion protein. Affinity, specificity, folding, and cooperativity: insights from circular dichroism. J Biol Chem vol. 278 (9), 6795-6802. 28-02-2003
2002
Dyson HJ, Wright PE, Mo HP and Viles JH (2002). Structure and dynamics of prion and doppel proteins. ABSTR PAP AM CHEM S vol. 223, C35-C35. 07-04-2002
Dyson HJ, Mo HP, Viles JH, Wright PE, Prusiner SB and Cohen FE (2002). Structure and dynamics of prion and Doppel proteins. BIOPHYS J vol. 82 (1), 169A-169A. 01-01-2002
2001
Viles JH, Duggan BM, Zaborowski E, Schwarzinger S, Huntley JJA, Kroon GJA, Dyson HJ and Wright PE (2001). Potential bias in NMR relaxation data introduced by peak intensity analysis and curve fitting methods. J BIOMOL NMR vol. 21 (1), 1-9. 01-09-2001
Viles JH, Donne D, Kroon G, Prusiner SB, Cohen FE, Dyson HJ and Wright PE (2001). Local structural plasticity of the prion protein. Analysis of NMR relaxation dynamics. BIOCHEMISTRY-US vol. 40 (9), 2743-2753. 06-03-2001
1999
Viles JH, Cohen FE, Prusiner SB, Goodin DB, Wright PE and Dyson HJ (1999). Copper binding to the prion protein: structural implications of four identical cooperative binding sites. Proc Natl Acad Sci U S A vol. 96 (5), 2042-2047. 02-03-1999
1998
Viles JH, Patel SU, Mitchell JB, Moody CM, Justice DE, Uppenbrink J, Doyle PM, Harris CJ, Sadler PJ and Thornton JM (1998). Design, synthesis and structure of a zinc finger with an artificial beta-turn. J Mol Biol vol. 279 (4), 973-986. 19-06-1998
1997
Donne DG, Viles JH, Groth D, Mehlhorn I, James TL, Cohen FE, Prusiner SB, Wright PE and Dyson HJ (1997). Structure of the recombinant full-length hamster prion protein PrP(29-231): the N terminus is highly flexible. Proc Natl Acad Sci U S A vol. 94 (25), 13452-13457. 09-12-1997
1996
Viles JH, Mitchell JB, Gough SL, Doyle PM, Harris CJ, Sadler PJ and Thornton JM (1996). Multiple solution conformations of the integrin-binding cyclic pentapeptide cyclo(-Ser-D-Leu-Asp-Val-Pro-). Analysis of the (phi, psi) space available to cyclic pentapeptides. Eur J Biochem vol. 242 (2), 352-362. 01-12-1996
Sadler PJ and Viles JH (1996). 1H and (113)Cd NMR Investigations of Cd(2+) and Zn(2+) Binding Sites on Serum Albumin: Competition with Ca(2+), Ni(2+), Cu(2+), and Zn(2+). Inorg Chem vol. 35 (15), 4490-4496. 17-07-1996
Harris R, Patel SU, Sadler PJ and Viles JH (1996). Observation of albumin resonances in proton nuclear magnetic resonance spectra of human blood plasma: N-terminal assignments aided by use of modified recombinant albumin. Analyst vol. 121 (7), 913-922. 01-07-1996
Doyle PM, Harris JC, Moody CM, Sadler PJ, Sims M, Thornton JM, Uppenbrink J and Viles JH (1996). Solution structure of a biologically active cyclic LDV peptide analogue containing a type II' beta-turn mimetic. Int J Pept Protein Res vol. 47 (6), 427-436. 01-06-1996
Jones DT, Moody CM, Uppenbrink J, Viles JH, Doyle PM, Harris CJ, Pearl LH, Sadler PJ and Thornton JM (1996). Towards meeting the Paracelsus Challenge: The design, synthesis, and characterization of paracelsin-43, an α-helical protein with over 50% sequence identity to an all-β protein. Proteins: Structure, Function and Genetics vol. 24 (4), 502-513. 03-05-1996
Jones DT, Moody CM, Uppenbrink J, Viles JH, Doyle PM, Harris CJ, Pearl LH, Sadler PJ and Thornton JM (1996). Towards meeting the Paracelsus Challenge: The design, synthesis, and characterization of paracelsin-43, an alpha-helical protein with over 50% sequence identity to an all-beta protein. Proteins vol. 24 (4), 502-513. 01-04-1996
Sadler PJ and Viles JH (1996). 1H and 113Cd NMR Investigations of Cd2+ and Zn2+ Binding Sites on Serum Albumin: Competition with Ca2+, Ni2+, Cu2+, and Zn2+. Inorganic Chemistry vol. 35 (15), 4490-4496. 01-01-1996
1994
Sadler PJ, Tucker A and Viles JH (1994). Involvement of a lysine residue in the N-terminal Ni2+ and Cu2+ binding site of serum albumins. Comparison with Co2+, Cd2+ and Al3+. Eur J Biochem vol. 220 (1), 193-200. 15-02-1994
1993
Patel SU, Sadler PJ, Tucker A and Viles JH (1993). Direct detection of albumin in human blood plasma by proton NMR spectroscopy. Complexation of nickel2+. Journal of the American Chemical Society, American Chemical Society (ACS) vol. 115 (20), 9285-9286. 01-10-1993
Grants of specific relevance to the Centre for Molecular Cell Biology
Amyloids and Oligomers. Curvilinear and annular structures and their interation with exosomes and whole cellsJohn Viles, Ivan Kadurin, Vladimir Volkov and Vidya Darbari
£485,209 BBSRC Biotechnology and Biological Sciences Research Council (01-12-2023 - 30-11-2026)