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, Alzheimers, 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
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 DiseaseTian Y, Shang Q, Liang R and Viles JH
Jacs Au, American Chemical Society (Acs) vol. 4 (2), 578-591.
06-02-2024
Impact of Membrane Phospholipids and Exosomes on the Kinetics of Amyloid-β Fibril AssemblyKhursheed A and Viles JH
Journal of Molecular Biology, Elsevier vol. 436 (6)
03-02-2024
2023
Imaging Amyloid‐β Membrane Interactions: Ion‐Channel Pores and Lipid‐Bilayer Permeability in Alzheimer's DiseaseViles JH
Angewandte Chemie, Wiley vol. 135 (25)
30-03-2023
2022
pH Dependence of Amyloid-β Fibril Assembly Kinetics: Unravelling the Microscopic Molecular Processes.Tian Y and Viles JH
Angewandte Chemie International Edition, Wiley
05-10-2022
pH Dependence of Amyloid‐β Fibril Assembly Kinetics: Unravelling the Microscopic Molecular ProcessesTian Y and Viles JH
Angewandte Chemie, Wiley
05-10-2022
Cross-seeding of WT amyloid-β with Arctic but not Italian familial mutants accelerates fibril formation in Alzheimer's diseaseLiang R, Tian Y and Viles JH
Journal of Biological Chemistry, American Society For Biochemistry and Molecular Biology vol. 298 (7)
01-07-2022
Therapeutic potential for amyloid surface inhibitor: only amyloid-β oligomers formed by secondary nucleation disrupt lipid membrane integrityTian Y, Liu J, Yang F, Lian C, Zhang H, Viles JH and Li Z
Febs Journal
19-06-2022
2021
3D-visualization of amyloid-β oligomer interactions with lipid membranes by cryo-electron tomographyTian Y, Liang R, Kumar A, Szwedziak P and Viles JH
Chemical Science, Royal Society of Chemistry vol. 12 (20), 6896-6907.
01-01-2021
2019
Copper2+ Binding to α-Synuclein. Histidine50 Can Form a Ternary Complex with Cu2+ at the N-Terminus but Not a Macrochelate.Tian Y, Stanyon HF, Barritt JD, Mayet U, Patel P, Karamani E, Fusco G and Viles JH
Inorganic Chemistry: Including Bioinorganic Chemistry, American Chemical Society vol. 58 (22), 15580-15589.
07-11-2019
Amyloid-β oligomers have a profound detergent-like effect on lipid membrane bilayers, imaged by atomic force and electron microscopy.Bode DC, Freeley M, Nield J, Palma M and Viles JH
J Biol Chem vol. 294 (19), 7566-7572.
10-05-2019
2018
Copper Redox Cycling Inhibits Aβ Fibre Formation and Promotes Fibre Fragmentation, while Generating a Dityrosine Aβ DimerVILES JH
Scientific Reports, Nature Publishing Group
01-11-2018
Prion protein stabilizes amyloid-β (Aβ) oligomers and enhances Aβ neurotoxicity in a Drosophila model of Alzheimer's disease.Younan ND, Chen K-F, Rose R-S, Crowther DC and Viles JH
J Biol Chem vol. 293 (34), 13090-13099.
24-08-2018
Serum Albumin's Protective Inhibition of Amyloid-β Fibre Formation Is Suppressed by Cholesterol, Fatty Acids and Warfarin.Bode DC, Stanyon HF, Hirani T, Baker MD, Nield J and Viles JH
J Mol Biol
02-02-2018
2017
N-Terminally Truncated Amyloid-β(11-40/42) Cofibrillizes with its Full-Length Counterpart: Implications for Alzheimer's Disease.Barritt JD, Younan ND and Viles JH
Angew Chem Int Ed Engl vol. 56 (33), 9816-9819.
07-08-2017
N‐Terminally Truncated Amyloid‐β(11–40/42) Cofibrillizes with its Full‐Length Counterpart: Implications for Alzheimer's DiseaseBarritt JD, Younan ND and Viles JH
Angewandte Chemie, Wiley vol. 129 (33), 9948-9951.
28-07-2017
2016
Ion Channel Formation by Amyloid-β42 Oligomers but not Amyloid-β40 in Cellular MembranesBAKER MD
Journal of Biological Chemistry, American Society For Biochemistry and Molecular Biology
07-12-2016
The Rapid Exchange of Zinc2+ Enables Trace Levels to Profoundly Influence Amyloid-β Misfolding and Dominates Assembly Outcomes in Cu2+/Zn2+ MixturesMatheou CJ, Younan ND and Viles JH
Journal of Molecular Biology vol. 428 (14), 2832-2846.
16-06-2016
Methionine oxidation reduces lag-times for Amyloid-β(1–40) fibre formation but generates highly fragmented fibresGu M and Viles JH
Biochimica Et Biophysica Acta (Bba) - Proteins and Proteomics
22-04-2016
Endocytosis of the tachykinin neuropeptide, neurokinin B, in astrocytes and its role in cellular copper uptakeShahzad R, Jones MR, Viles JH and Jones CE
Journal of Inorganic Biochemistry, Elsevier vol. 162, 319-325.
27-02-2016
2015
Truncated Amyloid-β(11–40/42) from Alzheimer Disease Binds Cu2+ with a Femtomolar Affinity and Influences Fiber Assembly*Barritt JD and Viles JH
Journal of Biological Chemistry, Elsevier vol. 290 (46), 27791-27802.
25-09-2015
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)Younan ND and Viles JH
Biochemistry, American Chemical Society (Acs) vol. 54 (28), 4297-4306.
10-07-2015
Amyloid β Protein and Alzheimer’s Disease: When Computer Simulations Complement Experimental StudiesNasica-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.
Chemical Reviews, American Chemical Society (Acs) vol. 115 (9), 3518-3563.
19-03-2015
Cu²⁺ accentuates distinct misfolding of Aβ₁₋₄₀ and Aβ₁₋₄₂ peptides, and potentiates membrane disruption.Matheou CJ, Younan ND and Viles JH
Biochemical Journal, Portland Press vol. 466 (2), 233-242.
20-02-2015
2014
Bioactivity and structural properties of chimeric analogs of the starfish SALMFamide neuropeptides S1 and S2.Jones CE, Otara CB, Younan ND, Viles JH and Elphick MR
Biochim Biophys Acta vol. 1844 (10), 1842-1850.
01-10-2014
Developing predictive rules for coordination geometry from visible circular dichroism of copper(II) and nickel(II) ions in histidine and amide main-chain complexes.Stanyon HF, Cong X, Chen Y, Shahidullah N, Rossetti G, Dreyer J, Papamokos G, Carloni P and Viles JH
Febs J vol. 281 (17), 3945-3954.
01-09-2014
Copper(II) sequentially loads onto the N-terminal amino group of the cellular prion protein before the individual octarepeats.Stanyon HF, Patel K, Begum N and Viles JH
Biochemistry vol. 53 (24), 3934-3999.
24-06-2014
Structural analysis of the starfish SALMFamide neuropeptides S1 and S2: the N-terminal region of S2 facilitates self-association.Otara CB, Jones CE, Younan ND, Viles JH and Elphick MR
Biochim Biophys Acta vol. 1844 (2), 358-365.
01-02-2014
2013
The cellular prion protein traps Alzheimer's Aβ in an oligomeric form and disassembles amyloid fibers.Younan ND, Sarell CJ, Davies P, Brown DR and Viles JH
Faseb J vol. 27 (5), 1847-1858.
01-05-2013
2012
Methionine oxidation perturbs the structural core of the prion protein and suggests a generic misfolding pathway.Younan ND, Nadal RC, Davies P, Brown DR and Viles JH
J Biol Chem vol. 287 (34), 28263-28275.
17-08-2012
Human serum albumin can regulate amyloid-β peptide fiber growth in the brain interstitium: implications for Alzheimer disease.Stanyon HF and Viles JH
J Biol Chem vol. 287 (33), 28163-28168.
10-08-2012
Metal ions and amyloid fiber formation in neurodegenerative diseases. Copper, zinc and iron in Alzheimer's, Parkinson's and prion diseasesViles JH
Coordination Chemistry Reviews vol. 256 (19-20), 2271-2284.
01-01-2012
2011
Copper(II)-induced secondary structure changes and reduced folding stability of the prion protein.Younan ND, Klewpatinond M, Davies P, Ruban AV, Brown DR and Viles JH
J Mol Biol vol. 410 (3), 369-382.
15-07-2011
The synucleins are a family of redox-active copper binding proteins.Davies P, Wang X, Sarell CJ, Drewett A, Marken F, Viles JH and Brown DR
Biochemistry vol. 50 (1), 37-47.
11-01-2011
2010
Substoichiometric levels of Cu2+ ions accelerate the kinetics of fiber formation and promote cell toxicity of amyloid-{beta} from Alzheimer disease.Sarell CJ, Wilkinson SR and Viles JH
J Biol Chem vol. 285 (53), 41533-41540.
31-12-2010
Is oxidation the trigger of the Amyloid Cascade?: A synthesis of 2-oxo-histidine for incorporation into the Amyloid beta sequence.Wright HM, Wyatt PB and Viles JH
J Pept Sci vol. 16, 66-66.
01-09-2010
2009
Evaluation of copper2+ affinities for the prion protein.Nadal RC, Davies P, Brown DR and Viles JH
Biochemistry vol. 48 (38), 8929-8931.
29-09-2009
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.Sarell CJ, Syme CD, Rigby SEJ and Viles JH
Biochemistry vol. 48 (20), 4388-4402.
26-05-2009
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.O'Sullivan DBD, Jones CE, Abdelraheim SR, Brazier MW, Toms H, Brown DR and Viles JH
Protein Sci vol. 18 (2), 410-423.
01-02-2009
2008
Copper and the structural biology of the prion protein.Viles JH, Klewpatinond M and Nadal RC
Biochem Soc Trans vol. 36 (Pt 6), 1288-1292.
01-12-2008
Amyloid beta-Cu2+ complexes in both monomeric and fibrillar forms do not generate H2O2 catalytically but quench hydroxyl radicals.Nadal RC, Rigby SEJ and Viles JH
Biochemistry vol. 47 (44), 11653-11664.
04-11-2008
Manganese binding to the prion protein.Brazier MW, Davies P, Player E, Marken F, Viles JH and Brown DR
J Biol Chem vol. 283 (19), 12831-12839.
09-05-2008
Deconvoluting the Cu2+ binding modes of full-length prion proteinKlewpatinond M, Davies P, Bowen S, Brown DR and Viles JH
J Biol Chem vol. 283 (4), 1870-1881.
25-01-2008
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 pHKlewpatinond M and Viles JH
Biochem J vol. 404, 393-402.
15-06-2007
Empirical rules for rationalising visible circular dichroism of Cu2+ and Ni2+ histidine complexes: Applications to the prion proteinKlewpatinond M and Viles JH
Febs Lett vol. 581 (7), 1430-1434.
03-04-2007
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.O'Sullivan DBD, Jones CE, Abdelraheim SR, Thompsett AR, Brazier MW, Toms H, Brown DR and Viles JH
Biochem J vol. 401 (2), 533-540.
15-01-2007
Prion protein does not redox-silence Cu2+, but is a sacrificial quencher of hydroxyl radicals.Nadal RC, Abdelraheim SR, Brazier MW, Rigby SEJ, Brown DR and Viles JH
Free Radic Biol Med vol. 42 (1), 79-89.
01-01-2007
2006
Solution 1H NMR investigation of Zn2+ and Cd2+ binding to amyloid-beta peptide (Abeta) of Alzheimer's disease.Syme CD and Viles JH
Biochim Biophys Acta vol. 1764 (2), 246-256.
01-02-2006
A survey of diamagnetic probes for copper2+ binding to the prion protein. 1H NMR solution structure of the palladium2+ bound single octarepeat.Garnett AP, Jones CE and Viles JH
Dalton Trans (3), 509-518.
21-01-2006
2005
Copper and the prion protein: Function and dysfunctionViles JH
The Biochemist, Portland Press vol. 27 (4), 9-12.
01-08-2005
Tertiary structure and activity of SALMFamide neuropeptidesOtara CB, Jones CE, Melarange R, Viles JH and Elphick MR
Comp Biochem Phys A vol. 141 (3), S161-S161.
01-07-2005
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.Jones CE, Klewpatinond M, Abdelraheim SR, Brown DR and Viles JH
J Mol Biol vol. 346 (5), 1393-1407.
11-03-2005
2004
Preferential Cu2+ coordination by His96 and His111 induces beta-sheet formation in the unstructured amyloidogenic region of the prion protein.Jones CE, Abdelraheim SR, Brown DR and Viles JH
J Biol Chem vol. 279 (31), 32018-32027.
30-07-2004
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.Syme CD, Nadal RC, Rigby SEJ and Viles JH
J Biol Chem vol. 279 (18), 18169-18177.
30-04-2004
2003
Copper binding to the octarepeats of the prion protein. Affinity, specificity, folding, and cooperativity: insights from circular dichroism.Garnett AP and Viles JH
J Biol Chem vol. 278 (9), 6795-6802.
28-02-2003
2002
Structure and dynamics of prion and doppel proteins.Dyson HJ, Wright PE, Mo HP and Viles JH
Abstr Pap Am Chem S vol. 223, C35-C35.
07-04-2002
Structure and dynamics of prion and Doppel proteinsDyson HJ, Mo HP, Viles JH, Wright PE, Prusiner SB and Cohen FE
Biophys J vol. 82 (1), 169A-169A.
01-01-2002
2001
Potential bias in NMR relaxation data introduced by peak intensity analysis and curve fitting methodsViles JH, Duggan BM, Zaborowski E, Schwarzinger S, Huntley JJA, Kroon GJA, Dyson HJ and Wright PE
J Biomol Nmr vol. 21 (1), 1-9.
01-09-2001
Local structural plasticity of the prion protein. Analysis of NMR relaxation dynamicsViles JH, Donne D, Kroon G, Prusiner SB, Cohen FE, Dyson HJ and Wright PE
Biochemistry-Us vol. 40 (9), 2743-2753.
06-03-2001
1999
Copper binding to the prion protein: structural implications of four identical cooperative binding sites.Viles JH, Cohen FE, Prusiner SB, Goodin DB, Wright PE and Dyson HJ
Proc Natl Acad Sci U S A vol. 96 (5), 2042-2047.
02-03-1999
1998
Design, synthesis and structure of a zinc finger with an artificial beta-turn.Viles JH, Patel SU, Mitchell JB, Moody CM, Justice DE, Uppenbrink J, Doyle PM, Harris CJ, Sadler PJ and Thornton JM
J Mol Biol vol. 279 (4), 973-986.
19-06-1998
1997
Structure of the recombinant full-length hamster prion protein PrP(29-231): the N terminus is highly flexible.Donne DG, Viles JH, Groth D, Mehlhorn I, James TL, Cohen FE, Prusiner SB, Wright PE and Dyson HJ
Proc Natl Acad Sci U S A vol. 94 (25), 13452-13457.
09-12-1997
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.Viles JH, Mitchell JB, Gough SL, Doyle PM, Harris CJ, Sadler PJ and Thornton JM
Eur J Biochem vol. 242 (2), 352-362.
01-12-1996
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+).Sadler PJ and Viles JH
Inorg Chem vol. 35 (15), 4490-4496.
17-07-1996
Observation of albumin resonances in proton nuclear magnetic resonance spectra of human blood plasma: N-terminal assignments aided by use of modified recombinant albumin.Harris R, Patel SU, Sadler PJ and Viles JH
Analyst vol. 121 (7), 913-922.
01-07-1996
Solution structure of a biologically active cyclic LDV peptide analogue containing a type II' beta-turn mimetic.Doyle PM, Harris JC, Moody CM, Sadler PJ, Sims M, Thornton JM, Uppenbrink J and Viles JH
Int J Pept Protein Res vol. 47 (6), 427-436.
01-06-1996
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 proteinJones DT, Moody CM, Uppenbrink J, Viles JH, Doyle PM, Harris CJ, Pearl LH, Sadler PJ and Thornton JM
Proteins: Structure, Function and Genetics vol. 24 (4), 502-513.
03-05-1996
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.Jones DT, Moody CM, Uppenbrink J, Viles JH, Doyle PM, Harris CJ, Pearl LH, Sadler PJ and Thornton JM
Proteins vol. 24 (4), 502-513.
01-04-1996
1H and 113Cd NMR Investigations of Cd2+ and Zn2+ Binding Sites on Serum Albumin: Competition with Ca2+, Ni2+, Cu2+, and Zn2+Sadler PJ and Viles JH
Inorganic Chemistry vol. 35 (15), 4490-4496.
01-01-1996
1994
Involvement of a lysine residue in the N-terminal Ni2+ and Cu2+ binding site of serum albumins. Comparison with Co2+, Cd2+ and Al3+.Sadler PJ, Tucker A and Viles JH
Eur J Biochem vol. 220 (1), 193-200.
15-02-1994
1993
Direct detection of albumin in human blood plasma by proton NMR spectroscopy. Complexation of nickel2+Patel SU, Sadler PJ, Tucker A and Viles JH
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 Chandran Darbari
£485,209 BBSRC Biotechnology and Biological Sciences Research Council
01-12-2023 - 30-11-2026