4xxd › Citations

Molecular basis for mid-region amyloid-β capture by leading Alzheimer's disease immunotherapies.

Crespi GA, Hermans SJ, Parker MW, Miles LA
Sci Rep 5 9649 (2015)
Cited: 48 times
EuropePMC logo PMID: 25880481

Abstract

Solanezumab (Eli Lilly) and crenezumab (Genentech) are the leading clinical antibodies targeting Amyloid-β (Aβ) to be tested in multiple Phase III clinical trials for the prevention of Alzheimer's disease in at-risk individuals. Aβ capture by these clinical antibodies is explained here with the first reported mid-region Aβ-anti-Aβ complex crystal structure. Solanezumab accommodates a large Aβ epitope (960 Å(2) buried interface over residues 16 to 26) that forms extensive contacts and hydrogen bonds to the antibody, largely via main-chain Aβ atoms and a deeply buried Phe19-Phe20 dipeptide core. The conformation of Aβ captured is an intermediate between observed sheet and helical forms with intramolecular hydrogen bonds stabilising residues 20-26 in a helical conformation. Remarkably, Aβ-binding residues are almost perfectly conserved in crenezumab. The structure explains the observed shared cross reactivity of solanezumab and crenezumab with proteins abundant in plasma that exhibit this Phe-Phe dipeptide.

Reviews - 4xxd mentioned but not cited (3)

  1. Passive immunotherapies targeting Aβ and tau in Alzheimer's disease. Plotkin SS, Cashman NR. Neurobiol Dis 144 105010 (2020)
  2. Conformational selection in amyloid-based immunotherapy: Survey of crystal structures of antibody-amyloid complexes. Ma B, Zhao J, Nussinov R. Biochim Biophys Acta 1860 2672-2681 (2016)
  3. Structural biology of cell surface receptors implicated in Alzheimer's disease. Hermans SJ, Nero TL, Morton CJ, Gooi JH, Crespi GAN, Hancock NC, Gao C, Ishii K, Markulić J, Parker MW. Biophys Rev 14 233-255 (2022)

Articles - 4xxd mentioned but not cited (8)

  1. Structure of Crenezumab Complex with Aβ Shows Loss of β-Hairpin. Ultsch M, Li B, Maurer T, Mathieu M, Adolfsson O, Muhs A, Pfeifer A, Pihlgren M, Bainbridge TW, Reichelt M, Ernst JA, Eigenbrot C, Fuh G, Atwal JK, Watts RJ, Wang W. Sci Rep 6 39374 (2016)
  2. Molecular basis for mid-region amyloid-β capture by leading Alzheimer's disease immunotherapies. Crespi GA, Hermans SJ, Parker MW, Miles LA. Sci Rep 5 9649 (2015)
  3. Antigen binding allosterically promotes Fc receptor recognition. Zhao J, Nussinov R, Ma B. MAbs 11 58-74 (2019)
  4. Mechanisms of recognition of amyloid-β (Aβ) monomer, oligomer, and fibril by homologous antibodies. Zhao J, Nussinov R, Ma B. J Biol Chem 292 18325-18343 (2017)
  5. Molecular Docking and Dynamic Simulation of AZD3293 and Solanezumab Effects Against BACE1 to Treat Alzheimer's Disease. Hassan M, Shahzadi S, Seo SY, Alashwal H, Zaki N, Moustafa AA. Front Comput Neurosci 12 34 (2018)
  6. Mutual population-shift driven antibody-peptide binding elucidated by molecular dynamics simulations. Bekker GJ, Fukuda I, Higo J, Kamiya N. Sci Rep 10 1406 (2020)
  7. Computational Analysis for the Rational Design of Anti-Amyloid Beta (Aβ) Antibodies. Greene D, Po T, Pan J, Tabibian T, Luo R. J Phys Chem B 122 4521-4536 (2018)
  8. Mechanism Exploration of Amyloid-β-42 Disaggregation by Single-Chain Variable Fragments of Alzheimer's Disease Therapeutic Antibodies. Fan X, Xu L, Zhang J, Wang Y, Wu Z, Sun W, Yao X, Wang X, Guan S, Shan Y. Int J Mol Sci 24 8371 (2023)


Reviews citing this publication (15)

  1. Amyloid beta: structure, biology and structure-based therapeutic development. Chen GF, Xu TH, Yan Y, Zhou YR, Jiang Y, Melcher K, Xu HE. Acta Pharmacol Sin 38 1205-1235 (2017)
  2. Protein misfolding in neurodegenerative diseases: implications and strategies. Sweeney P, Park H, Baumann M, Dunlop J, Frydman J, Kopito R, McCampbell A, Leblanc G, Venkateswaran A, Nurmi A, Hodgson R. Transl Neurodegener 6 6 (2017)
  3. Anti-Amyloid-β Monoclonal Antibodies for Alzheimer's Disease: Pitfalls and Promise. van Dyck CH. Biol Psychiatry 83 311-319 (2018)
  4. Passive Aβ Immunotherapy: Current Achievements and Future Perspectives. Schilling S, Rahfeld JU, Lues I, Lemere CA. Molecules 23 E1068 (2018)
  5. Structural metamorphism and polymorphism in proteins on the brink of thermodynamic stability. Kulkarni P, Solomon TL, He Y, Chen Y, Bryan PN, Orban J. Protein Sci 27 1557-1567 (2018)
  6. Aβ-Immunotherapeutic strategies: a wide range of approaches for Alzheimer's disease treatment. Montoliu-Gaya L, Villegas S. Expert Rev Mol Med 18 e13 (2016)
  7. Current progress, challenges and future prospects of diagnostic and therapeutic interventions in Alzheimer's disease. Rajasekhar K, Govindaraju T. RSC Adv 8 23780-23804 (2018)
  8. Passive Immunotherapies Targeting Amyloid Beta and Tau Oligomers in Alzheimer's Disease. Vander Zanden CM, Chi EY. J Pharm Sci 109 68-73 (2020)
  9. Antibody Engineering for Optimized Immunotherapy in Alzheimer's Disease. Sumner IL, Edwards RA, Asuni AA, Teeling JL. Front Neurosci 12 254 (2018)
  10. An Overview of Several Inhibitors for Alzheimer's Disease: Characterization and Failure. Boopathi S, Poma AB, Garduño-Juárez R. Int J Mol Sci 22 10798 (2021)
  11. Aβ and the dementia syndrome: Simple versus complex perspectives. Hunter S, Smailagic N, Brayne C. Eur J Clin Invest 48 e13025 (2018)
  12. Structure and Function of Alzheimer's Amyloid βeta Proteins from Monomer to Fibrils: A Mini Review. Agrawal N, Skelton AA. Protein J 38 425-434 (2019)
  13. Invasive and non-invasive therapies for Alzheimer's disease and other amyloidosis. Pandey G, Ramakrishnan V. Biophys Rev 12 1175-1186 (2020)
  14. Review of Advanced Drug Trials Focusing on the Reduction of Brain Beta-Amyloid to Prevent and Treat Dementia. Decourt B, Noorda K, Noorda K, Shi J, Sabbagh MN. J Exp Pharmacol 14 331-352 (2022)
  15. Symptomatic and Disease-Modifying Therapy Pipeline for Alzheimer's Disease: Towards a Personalized Polypharmacology Patient-Centered Approach. Morató X, Pytel V, Jofresa S, Ruiz A, Boada M. Int J Mol Sci 23 9305 (2022)

Articles citing this publication (22)

  1. MX2: a high-flux undulator microfocus beamline serving both the chemical and macromolecular crystallography communities at the Australian Synchrotron. Aragão D, Aishima J, Cherukuvada H, Clarken R, Clift M, Cowieson NP, Ericsson DJ, Gee CL, Macedo S, Mudie N, Panjikar S, Price JR, Riboldi-Tunnicliffe A, Rostan R, Williamson R, Caradoc-Davies TT. J Synchrotron Radiat 25 885-891 (2018)
  2. Kinetic fingerprints differentiate the mechanisms of action of anti-Aβ antibodies. Linse S, Scheidt T, Bernfur K, Vendruscolo M, Dobson CM, Cohen SIA, Sileikis E, Lundqvist M, Qian F, O'Malley T, Bussiere T, Weinreb PH, Xu CK, Meisl G, Devenish SRA, Knowles TPJ, Hansson O. Nat Struct Mol Biol 27 1125-1133 (2020)
  3. Abeta targets of the biosimilar antibodies of Bapineuzumab, Crenezumab, Solanezumab in comparison to an antibody against N‑truncated Abeta in sporadic Alzheimer disease cases and mouse models. Bouter Y, Lopez Noguerola JS, Tucholla P, Crespi GA, Parker MW, Wiltfang J, Miles LA, Bayer TA. Acta Neuropathol 130 713-729 (2015)
  4. Inhibiting amyloid-β cytotoxicity through its interaction with the cell surface receptor LilrB2 by structure-based design. Cao Q, Shin WS, Chan H, Vuong CK, Dubois B, Li B, Murray KA, Sawaya MR, Feigon J, Black DL, Eisenberg DS, Jiang L. Nat Chem 10 1213-1221 (2018)
  5. The interaction with gold suppresses fiber-like conformations of the amyloid β (16-22) peptide. Bellucci L, Ardèvol A, Parrinello M, Lutz H, Lu H, Weidner T, Corni S. Nanoscale 8 8737-8748 (2016)
  6. N-terminal heterogeneity of parenchymal and vascular amyloid-β deposits in Alzheimer's disease. Zampar S, Klafki HW, Sritharen K, Bayer TA, Wiltfang J, Rostagno A, Ghiso J, Miles LA, Wirths O. Neuropathol Appl Neurobiol 46 673-685 (2020)
  7. High-affinity Anticalins with aggregation-blocking activity directed against the Alzheimer β-amyloid peptide. Rauth S, Hinz D, Börger M, Uhrig M, Mayhaus M, Riemenschneider M, Skerra A. Biochem J 473 1563-1578 (2016)
  8. Ex vivo 18O-labeling mass spectrometry identifies a peripheral amyloid β clearance pathway. Portelius E, Mattsson N, Pannee J, Zetterberg H, Gisslén M, Vanderstichele H, Gkanatsiou E, Crespi GA, Parker MW, Miles LA, Gobom J, Blennow K. Mol Neurodegener 12 18 (2017)
  9. Fibrillation-prone conformations of the amyloid-β-42 peptide at the gold/water interface. Bellucci L, Bussi G, Di Felice R, Corni S. Nanoscale 9 2279-2290 (2017)
  10. Amyloid binding and beyond: a new approach for Alzheimer's disease drug discovery targeting Aβo-PrPC binding and downstream pathways. Grayson JD, Baumgartner MP, Santos Souza CD, Dawes SJ, El Idrissi IG, Louth JC, Stimpson S, Mead E, Dunbar C, Wolak J, Sharman G, Evans D, Zhuravleva A, Roldan MS, Colabufo NA, Ning K, Garwood C, Thomas JA, Partridge BM, de la Vega de Leon A, Gillet VJ, Rauter AP, Chen B. Chem Sci 12 3768-3785 (2021)
  11. Solution-Based Determination of Dissociation Constants for the Binding of Aβ42 to Antibodies. Zhang T, Zhang T, Nagel-Steger L, Willbold D. ChemistryOpen 8 989-994 (2019)
  12. Dynamic Docking Using Multicanonical Molecular Dynamics: Simulating Complex Formation at the Atomistic Level. Bekker GJ, Kamiya N. Methods Mol Biol 2266 187-202 (2021)
  13. Published Erratum Erratum to: Do anti-amyloid beta protein antibody cross reactivities confound Alzheimer disease research? Hunter S, Brayne C. J Negat Results Biomed 16 8 (2017)
  14. Quantitative systems pharmacology model of the amyloid pathway in Alzheimer's disease: Insights into the therapeutic mechanisms of clinical candidates. Ramakrishnan V, Friedrich C, Witt C, Sheehan R, Pryor M, Atwal JK, Wildsmith K, Kudrycki K, Lee SH, Mazer N, Hofmann C, Fuji RN, Jin JY, Ramanujan S, Dolton M, Quartino A. CPT Pharmacometrics Syst Pharmacol 12 62-73 (2023)
  15. Alzheimer's Aβ1-40 peptide degradation by thermolysin: evidence of inhibition by a C-terminal Aβ product. Leite JP, Gales L. FEBS Lett 593 128-137 (2019)
  16. Amyloid in the ageing brain: New frameworks and perspectives. Hunter S, Brayne C. Aging Brain 1 100008 (2021)
  17. Antibody binding of amyloid beta peptide epimers/isomers and ramifications for immunotherapies and drug development. Readel ER, Patel A, Putman JI, Du S, Armstrong DW. Sci Rep 13 12387 (2023)
  18. Antibody-guided proteases enable selective and catalytic degradation of challenging therapeutic targets. Romei MG, Leonard B, Kim I, Kim HS, Lazar GA. J Biol Chem 299 104685 (2023)
  19. Blood-brain barrier penetrating neprilysin degrades monomeric amyloid-beta in a mouse model of Alzheimer's disease. Rofo F, Metzendorf NG, Saubi C, Suominen L, Godec A, Sehlin D, Syvänen S, Hultqvist G. Alzheimers Res Ther 14 180 (2022)
  20. Characterization of Amyloidogenic Peptide Aggregability in Helical Subspace. Bhattacharya S, Xu L, Thompson D. Methods Mol Biol 2340 401-448 (2022)
  21. Epitope Mapping by NMR of a Novel Anti-Aβ Antibody (STAB-MAb). Posado-Fernández A, Afonso CF, Dória G, Flores O, Cabrita EJ. Sci Rep 9 12241 (2019)
  22. Identification of Catechins' Binding Sites in Monomeric Aβ42 through Ensemble Docking and MD Simulations. Firouzi R, Sowlati-Hashjin S, Chávez-García C, Ashouri M, Karimi-Jafari MH, Karttunen M. Int J Mol Sci 24 8161 (2023)


Quick links