Structural effects of the highly protective V127 polymorphism on human prion protein.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
29 07 2020
29 07 2020
Historique:
received:
23
10
2019
accepted:
03
07
2020
entrez:
31
7
2020
pubmed:
31
7
2020
medline:
16
6
2021
Statut:
epublish
Résumé
Prion diseases, a group of incurable, lethal neurodegenerative disorders of mammals including humans, are caused by prions, assemblies of misfolded host prion protein (PrP). A single point mutation (G127V) in human PrP prevents prion disease, however the structural basis for its protective effect remains unknown. Here we show that the mutation alters and constrains the PrP backbone conformation preceding the PrP β-sheet, stabilising PrP dimer interactions by increasing intermolecular hydrogen bonding. It also markedly changes the solution dynamics of the β2-α2 loop, a region of PrP structure implicated in prion transmission and cross-species susceptibility. Both of these structural changes may affect access to protein conformers susceptible to prion formation and explain its profound effect on prion disease.
Identifiants
pubmed: 32728168
doi: 10.1038/s42003-020-01126-6
pii: 10.1038/s42003-020-01126-6
pmc: PMC7391680
doi:
Substances chimiques
Prion Proteins
0
Prions
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
402Subventions
Organisme : Medical Research Council
ID : MC_UU_00024/9
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U123170362
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00024/6
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M02492X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U117533887
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U123160657
Pays : United Kingdom
Références
Prusiner, S. B. Prions. Proc. Natl Acad. Sci. USA 95, 13363–13383 (1998).
pubmed: 9811807
doi: 10.1073/pnas.95.23.13363
Collinge, J. & Clarke, A. A general model of prion strains and their pathogenicity. Science 318, 930–936 (2007).
pubmed: 17991853
doi: 10.1126/science.1138718
Terry, C. et al. Ex vivo mammalian prions are formed of paired double helical prion protein fibrils. Open Biol. 6, 160035 (2016).
pubmed: 27249641
pmcid: 4892434
doi: 10.1098/rsob.160035
Terry, C. et al. Structural features distinguishing infectious ex vivo mammalian prions from non-infectious fibrillar assemblies generated in vitro. Sci. Rep. 9, 376 (2019).
pubmed: 30675000
pmcid: 6344479
doi: 10.1038/s41598-018-36700-w
Griffith, J. S. Self replication and scrapie. Nature 215, 1043–1044 (1967).
pubmed: 4964084
doi: 10.1038/2151043a0
Eisenberg, D. & Jucker, M. The amyloid state of proteins in human diseases. Cell 148, 1188–1203 (2012).
pubmed: 22424229
pmcid: 3353745
doi: 10.1016/j.cell.2012.02.022
Jaunmuktane, Z. et al. Evidence for human transmission of amyloid-beta pathology and cerebral amyloid angiopathy. Nature 525, 247–250 (2015).
pubmed: 26354483
doi: 10.1038/nature15369
Purro, S. A. et al. Transmission of amyloid-beta protein pathology from cadaveric pituitary growth hormone. Nature 564, 415–419 (2018).
pubmed: 30546139
pmcid: 6708408
doi: 10.1038/s41586-018-0790-y
Jucker, M. & Walker, L. C. Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature 501, 45–51 (2013).
pubmed: 24005412
pmcid: 3963807
doi: 10.1038/nature12481
Walker, L. C. & Jucker, M. Neurodegenerative diseases: expanding the prion concept. Annu. Rev. Neurosci. 38, 87–103 (2015).
pubmed: 25840008
pmcid: 4803040
doi: 10.1146/annurev-neuro-071714-033828
Collinge, J. Mammalian prions and their wider relevance in neurodegenerative diseases. Nature 539, 217–226 (2016).
pubmed: 27830781
doi: 10.1038/nature20415
Bolton, D. C., McKinley, M. P. & Prusiner, S. B. Identification of a protein that purifies with the scrapie prion. Science 218, 1309–1311 (1982).
pubmed: 6815801
doi: 10.1126/science.6815801
Meyer, R. K. et al. Separation and properties of cellular and scrapie prion proteins. Proc. Natl. Acad. Sci. USA 83, 2310–2314 (1986).
pubmed: 3085093
doi: 10.1073/pnas.83.8.2310
Collinge, J. Prion diseases of humans and animals: their causes and molecular basis. Annu. Rev. Neurosci. 24, 519–550 (2001).
pubmed: 11283320
doi: 10.1146/annurev.neuro.24.1.519
Wadsworth, J. D., Asante, E. A. & Collinge, J. Contribution of transgenic models to understanding human prion disease. Neuropathol. Appl. Neurobiol. 36, 576–597 (2010).
pubmed: 20880036
pmcid: 3017745
doi: 10.1111/j.1365-2990.2010.01129.x
Collinge, J. Variant Creutzfeldt-Jakob disease. Lancet 354, 317–323 (1999).
pubmed: 10440324
doi: 10.1016/S0140-6736(99)05128-4
Collinge, J. Molecular neurology of prion disease. J. Neurol. Neurosurg. Psychiatry 76, 906–919 (2005).
pubmed: 15965195
pmcid: 1739714
doi: 10.1136/jnnp.2004.048660
Asante, E. A. et al. Dissociation of pathological and molecular phenotype of variant Creutzfeldt-Jakob disease in transgenic human prion protein 129 heterozygous mice. Proc. Natl. Acad. Sci. USA 103, 10759–10764 (2006).
pubmed: 16809423
doi: 10.1073/pnas.0604292103
Mead, S. et al. Genetic risk factors for variant Creutzfeldt-Jakob disease: a genome-wide association study. Lancet Neurol. 8, 57–66 (2009).
pubmed: 19081515
pmcid: 2643048
doi: 10.1016/S1474-4422(08)70265-5
Wadsworth, J. D. & Collinge, J. Molecular pathology of human prion disease. Acta Neuropathol. 121, 69–77 (2011).
pubmed: 20694796
doi: 10.1007/s00401-010-0735-5
Collinge, J., Sidle, K. C., Meads, J., Ironside, J. & Hill, A. F. Molecular analysis of prion strain variation and the aetiology of ‘new variant’ CJD. Nature 383, 685–690 (1996).
pubmed: 8878476
doi: 10.1038/383685a0
Hosszu, L. L. P. et al. The residue 129 polymorphism in human prion protein does not confer susceptibility to CJD by altering the structure or global stability of PrP
pubmed: 15123682
doi: 10.1074/jbc.M313762200
Mead, S. et al. Balancing selection at the prion protein gene consistent with prehistoric kuru-like epidemics. Science 300, 640–643 (2003).
pubmed: 12690204
doi: 10.1126/science.1083320
Mead, S. et al. A novel protective prion protein variant that colocalizes with kuru exposure. New Engl. J. Med 361, 2056–2065 (2009).
pubmed: 19923577
doi: 10.1056/NEJMoa0809716
Asante, E. A. et al. A naturally occurring variant of the human prion protein completely prevents prion disease. Nature 522, 478–481 (2015).
pubmed: 26061765
pmcid: 4486072
doi: 10.1038/nature14510
Sigurdson, C. J. et al. A molecular switch controls interspecies prion disease transmission in mice. J. Clin. Invest. 120, 2590–2599 (2010).
pubmed: 20551516
pmcid: 2898603
doi: 10.1172/JCI42051
Christen, B., Damberger, F. F., Perez, D. R., Hornemann, S. & Wuthrich, K. Structural plasticity of the cellular prion protein and implications in health and disease. Proc. Natl. Acad. Sci. USA 110, 8549–8554 (2013).
pubmed: 23650394
doi: 10.1073/pnas.1306178110
Kurt, T. D. et al. Prion transmission prevented by modifying the β2-α2 loop structure of Host PrPC. J. Neurosci. 34, 1022–1027 (2014).
pubmed: 24431459
pmcid: 3891945
doi: 10.1523/JNEUROSCI.4636-13.2014
Antonyuk, S. V. et al. Crystal structure of human prion protein bound to a therapeutic antibody. Proc. Natl. Acad. Sci. USA 106, 2554–2558 (2009).
pubmed: 19204296
doi: 10.1073/pnas.0809170106
Haire, L. F. et al. The crystal structure of the globular domain of sheep prion protein. J. Mol. Biol. 336, 1175–1183 (2004).
pubmed: 15037077
doi: 10.1016/j.jmb.2003.12.059
Khan, M. Q. et al. Prion disease susceptibility is affected by beta-structure folding propensity and local side-chain interactions in PrP. Proc. Natl. Acad. Sci. USA 107, 19808–19813 (2010).
pubmed: 21041683
doi: 10.1073/pnas.1005267107
Lee, S. et al. Conformational diversity in prion protein variants influences intermolecular beta-sheet formation. EMBO J. 29, 251–262 (2010).
pubmed: 19927125
doi: 10.1038/emboj.2009.333
Zhou, S., Shi, D., Liu, X., Liu, H. & Yao, X. Protective V127 prion variant prevents prion disease by interrupting the formation of dimer and fibril from molecular dynamics simulations. Sci. Rep. 6, 21804 (2016).
pubmed: 26906032
pmcid: 4764842
doi: 10.1038/srep21804
Zheng, Z. et al. Structural basis for the complete resistance of the human prion protein mutant G127V to prion disease. Sci. Rep. 8, 13211 (2018).
pubmed: 30181558
pmcid: 6123418
doi: 10.1038/s41598-018-31394-6
Watts, J. C. et al. Evidence that bank vole PrP is a universal acceptor for prions. PLoS Pathog. 10, e1003990 (2014).
pubmed: 24699458
pmcid: 3974871
doi: 10.1371/journal.ppat.1003990
Kurt, T. D., Jiang, L., Bett, C., Eisenberg, D. & Sigurdson, C. J. A proposed mechanism for the promotion of prion conversion involving a strictly conserved tyrosine residue in the β2-α2 loop of PrPC. J. Biol. Chem. 289, 10660–10667 (2014).
pubmed: 24596090
pmcid: 4036184
doi: 10.1074/jbc.M114.549030
Goldfarb, L. G. et al. Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by a DNA polymorphism. Science 258, 806–808 (1992).
pubmed: 1439789
doi: 10.1126/science.1439789
d’Auvergne, E. J. & Gooley, P. R. Optimisation of NMR dynamic models I. Minimisation algorithms and their performance within the model-free and Brownian rotational diffusion spaces. J. Biomol. NMR 40, 107–119 (2008).
pubmed: 18085410
doi: 10.1007/s10858-007-9214-2
d’Auvergne, E. J. & Gooley, P. R. Optimisation of NMR dynamic models II. A new methodology for the dual optimisation of the model-free parameters and the Brownian rotational diffusion tensor. J. Biomol. NMR 40, 121–133 (2008).
pubmed: 18085411
doi: 10.1007/s10858-007-9213-3
Damberger, F. F., Christen, B., Perez, D. R., Hornemann, S. & Wuthrich, K. Cellular prion protein conformation and function. Proc. Natl. Acad. Sci. USA 108, 17308–17313 (2011).
pubmed: 21987789
doi: 10.1073/pnas.1106325108
Abskharon, R. N. et al. Probing the N-terminal beta-sheet conversion in the crystal structure of the human prion protein bound to a nanobody. J. Am. Chem. Soc. 136, 937–944 (2014).
pubmed: 24400836
doi: 10.1021/ja407527p
Fu, Z. L., Holmes, P. C., Westaway, D. & Sykes, B. D. Nascent β structure in the elongated hydrophobic region of a gerstmann-straussler-scheinker PrP allele. J. Mol. Biol. 431, 2599–2611 (2019).
pubmed: 31034890
doi: 10.1016/j.jmb.2019.04.027
Hosszu, L. L. P. et al. Structural mobility of the human prion protein probed by backbone hydrogen exchange. Nat. Struct. Biol. 6, 740–743 (1999).
pubmed: 10426950
doi: 10.1038/11507
Baskakov, I. et al. The presence of valine at residue 129 in human prion protein accelerates amyloid formation. FEBS Lett. 579, 2589–2596 (2005).
pubmed: 15862295
doi: 10.1016/j.febslet.2005.03.075
Tartaglia, G. G. et al. Prediction of aggregation-prone regions in structured proteins. J. Mol. Biol. 380, 425–436 (2008).
pubmed: 18514226
doi: 10.1016/j.jmb.2008.05.013
Sabareesan, A. T. & Udgaonkar, J. B. The G126V mutation in the mouse prion protein hinders nucleation dependent fibril formation by slowing down initial fibril growth and by increasing the critical concentration. Biochemistry 56, 5931–5942 (2017).
pubmed: 29045139
doi: 10.1021/acs.biochem.7b00894
Saborio, G. P., Permanne, B. & Soto, C. Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 411, 810–813 (2001).
pubmed: 11459061
doi: 10.1038/35081095
Palmer, M. S., Dryden, A. J., Hughes, J. T. & Collinge, J. Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease. Nature 352, 340–342 (1991).
pubmed: 1677164
doi: 10.1038/352340a0
Bhattacharya, A., Tejero, R. & Montelione, G. T. Evaluating protein structures determined by structural genomics consortia. Proteins 66, 778–795 (2007).
pubmed: 17186527
doi: 10.1002/prot.21165
Priola, S. A., Caughey, B., Wehrly, K. & Chesebro, B. A 60-kDa prion protein (PrP) with properties of both the normal and scrapie-associated forms of PrP. J. Biol. Chem. 270, 3299–3305 (1995).
pubmed: 7852415
doi: 10.1074/jbc.270.7.3299
Meyer, R. K. et al. A monomer-dimer equilibrium of a cellular prion protein (PrP
pubmed: 10967124
doi: 10.1074/jbc.M007114200
Rambold, A. S. et al. Stress-protective signalling of prion protein is corrupted by scrapie prions. EMBO J. 27, 1974–1984 (2008).
pubmed: 18566584
pmcid: 2486277
doi: 10.1038/emboj.2008.122
Meier, P. et al. Soluble dimeric prion protein binds PrP(Sc) in vivo and antagonizes prion disease. Cell 113, 49–60 (2003).
pubmed: 12679034
doi: 10.1016/S0092-8674(03)00201-0
Engelke, A. D. et al. Dimerization of the cellular prion protein inhibits propagation of scrapie prions. J. Biol. Chem. 293, 8020–8031 (2018).
pubmed: 29636413
pmcid: 5971439
doi: 10.1074/jbc.RA117.000990
Abskharon, R. et al. Structural evidence for the critical role of the prion protein hydrophobic region in forming an infectious prion. PLoS Pathog. 15, e1008139 (2019).
pubmed: 31815959
pmcid: 6922452
doi: 10.1371/journal.ppat.1008139
Somerville, R. A. et al. Characterization of thermodynamic diversity between transmissible spongiform encephalopathy agent strains and its theoretical implications. J. Biol. Chem. 277, 11084–11089 (2002).
pubmed: 11792707
doi: 10.1074/jbc.M111766200
Somerville, R. A. & Gentles, N. Characterisation of the effect of heat on agent-strains of the transmissible spongiform encephalopathies. J. Gen. Virol. 92, 1738–1748 (2011).
pubmed: 21471321
doi: 10.1099/vir.0.030452-0
Leske, H. et al. Protease resistance of infectious prions is suppressed by removal of a single atom in the cellular prion protein. PLoS ONE 12, e0170503 (2017).
pubmed: 28207746
pmcid: 5313174
doi: 10.1371/journal.pone.0170503
Telling, G. C. et al. Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of cellular PrP with another protein. Cell 83, 79–90 (1995).
pubmed: 7553876
doi: 10.1016/0092-8674(95)90236-8
Kaneko, K. et al. Evidence for protein X binding to a discontinuous epitope on the cellular prion protein during scrapie prion propagation. Proc. Natl. Acad. Sci. USA 94, 10069–10074 (1997).
pubmed: 9294164
doi: 10.1073/pnas.94.19.10069
Shibuya, S., Higuchi, J., Shin, R. W., Tateishi, J. & Kitamoto, T. Codon 219 Lys allele of PRNP is not found in sporadic Creutzfeldt-Jakob disease. Ann. Neurol. 43, 826–828 (1998).
pubmed: 9629853
doi: 10.1002/ana.410430618
Perrier, V. et al. Dominant-negative inhibition of prion replication in transgenic mice. Proc. Natl. Acad. Sci. USA 99, 13079–13084 (2002).
pubmed: 12271119
doi: 10.1073/pnas.182425299
Beck, J. A. et al. PRNP allelic series from 19 years of prion protein gene sequencing at the MRC Prion Unit. Hum. Mutat. 31, E1551–E1563 (2010).
pubmed: 20583301
doi: 10.1002/humu.21281
Jansen, C. et al. A second case of gerstmann-straussler-scheinker disease linked to the G131V mutation in the prion protein gene in a dutch patient. J. Neuropathol. Exp. Neurol. 70, 698–702 (2011).
pubmed: 21760536
doi: 10.1097/NEN.0b013e3182270c54
Clouscard, C. et al. Different allelic effects of the codons 136 and 171 of the prion protein gene in sheep with natural scrapie. J. Gen. Virol. 76, 2097–2101 (1995).
pubmed: 7636494
doi: 10.1099/0022-1317-76-8-2097
Geoghegan, J. C., Miller, M. B., Kwak, A. H., Harris, B. T. & Supattapone, S. Trans-dominant inhibition of prion propagation in vitro is not mediated by an accessory cofactor. PLoS Pathog. 5, e1000535 (2009).
pubmed: 19649330
pmcid: 2713408
doi: 10.1371/journal.ppat.1000535
Anandakrishnan, R., Aguilar, B. F., & Onufriev, A. V. H++ 3.0: automating pK prediction and the preparation of biomolecular structures for atomistic molecular modeling and simulations. Nucleic Acids Res. 40, W537–41(2012).
Karamanos, T. K., Kalverda, A. P., Thompson, G. S. & Radford, S. E. Visualization of transient protein-protein interactions that promote or inhibit amyloid assembly. Mol. Cell 55, 214–226 (2014).
pubmed: 24981172
pmcid: 4104025
doi: 10.1016/j.molcel.2014.05.026
Hosszu, L. L. P. et al. Definable equilibrium states in the folding of human prion protein. Biochemistry 44, 16649–16657 (2005).
pubmed: 16342955
doi: 10.1021/bi051277k
Viles, J. H. et al. Local structural plasticity of the prion protein. Analysis of NMR relaxation dynamics. Biochemistry 40, 2743–2753 (2001).
pubmed: 11258885
doi: 10.1021/bi002898a
Bae, S. H. et al. Prion proteins with pathogenic and protective mutations show similar structure and dynamics. Biochemistry 48, 8120–8128 (2009).
pubmed: 19618915
pmcid: 2762478
doi: 10.1021/bi900923b
Zahn, R. et al. NMR solution structure of the human prion protein. Proc. Natl. Acad. Sci. USA 97, 145–150 (2000).
pubmed: 10618385
doi: 10.1073/pnas.97.1.145
O’sullivan, D. B. et al. 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. 18, 410–423 (2008).
doi: 10.1002/pro.44
Kabsch, W. XDS. Acta Crystallogr. D Biol. Crystallogr. 66, 125–132 (2010).
pubmed: 20124692
pmcid: 2815665
doi: 10.1107/S0907444909047337
Foadi, J. et al. Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography. Acta Crystallogr. D Biol. Crystallogr. 69, 1617–1632 (2013).
pubmed: 23897484
pmcid: 3727331
doi: 10.1107/S0907444913012274
Evans, P. R. & Murshudov, G. N. How good are my data and what is the resolution? Acta Crystallogr. D Biol. Crystallogr. 69, 1204–1214 (2013).
pubmed: 23793146
pmcid: 3689523
doi: 10.1107/S0907444913000061
McCoy, A. J. et al. Phaser crystallographic software. J. Appl Crystallogr. 40, 658–674 (2007).
pubmed: 19461840
pmcid: 2483472
doi: 10.1107/S0021889807021206
Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126–2132 (2004).
doi: 10.1107/S0907444904019158
Murshudov, G. N. et al. REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr. D Biol. Crystallogr. 67, 355–367 (2011).
pubmed: 21460454
pmcid: 3069751
doi: 10.1107/S0907444911001314
Laskowski, R. A., Macarthur, M. W., Moss, D. S. & Thornton, J. M. Procheck - a program to check the stereochemical quality of protein structures. J. Appl. Crystallogr. 26, 283–291 (1993).
doi: 10.1107/S0021889892009944
Bodenhausen, G. & Ruben, D. J. Natural abundance N-15 Nmr by enhanced heteronuclear spectroscopy. Chem. Phys. Lett. 69, 185–189 (1980).
doi: 10.1016/0009-2614(80)80041-8
Schleucher, J. et al. A general enhancement scheme in heteronuclear multidimensional NMR employing pulsed field gradients. J. Biomol. NMR 4, 301–306 (1994).
pubmed: 8019138
doi: 10.1007/BF00175254
Bax, A. & Grzesiek, S. Methodological advances in protein Nmr. Acc. Chem. Res. 26, 131–138 (1993).
doi: 10.1021/ar00028a001
Wishart, D. S., Sykes, B. D. & Richards, F. M. Relationship between nuclear magnetic resonance chemical shift and protein secondary structure. J. Mol. Biol. 222, 311–333 (1991).
pubmed: 1960729
doi: 10.1016/0022-2836(91)90214-Q
Vranken, W. F. et al. The CCPN data model for NMR spectroscopy: development of a software pipeline. Proteins 59, 687–696 (2005).
pubmed: 15815974
doi: 10.1002/prot.20449
Yip, G. N. & Zuiderweg, E. R. Improvement of duty-cycle heating compensation in NMR spin relaxation experiments. J. Magn. Reson. 176, 171–178 (2005).
pubmed: 16009587
doi: 10.1016/j.jmr.2005.06.003
Lipari, G. & Szabo, A. Model-free approach to the interpretation of nuclear magnetic-resonance relaxation in macromolecules.1. Theory and range of validity. J. Am. Chem. Soc. 104, 4546–4559 (1982).
doi: 10.1021/ja00381a009
Bai, Y., Milne, J. S., Mayne, L. & Englander, S. W. Primary structure effects on peptide group hydrogen exchange. Proteins 17, 75–86 (1993).
pubmed: 8234246
pmcid: 3438223
doi: 10.1002/prot.340170110
Parker, M. J., Spencer, J. & Clarke, A. R. An integrated kinetic analysis of intermediates and transition states in protein folding reactions. J. Mol. Biol. 253, 771–786 (1995).
pubmed: 7473751
doi: 10.1006/jmbi.1995.0590
Nielsen, L., Frokjaer, S., Brange, J., Uversky, V. N. & Fink, A. L. Probing the mechanism of insulin fibril formation with insulin mutants. Biochemistry 40, 8397–8409 (2001).
pubmed: 11444987
doi: 10.1021/bi0105983