4xxd › Citations

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

<div class='caption-title'>Structure of the mid-region of the Aβ peptide bound to solanezumab.</div>
<div class='caption-title'>The clinical antibodies solanezumab and crenezumab recognise Aβ in almost identical fashion.</div>
<div class='caption-title'>Different conformations of the mid-region of the Aβ peptide.</div>
Crespi GA, Hermans SJ, Parker MW, Miles LA
OpenAccess logo Sci Rep 5 9649 (2015)
Cited: 52 times
EuropePMC logo PMID:
doi logo

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. Plotkin SS, Cashman NR. Neurobiol Dis 144 105010 (2020)
  2. Ma B, Zhao J, Nussinov R. Biochim Biophys Acta 1860 2672-2681 (2016)
  3. 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 (9)

  1. 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. Crespi GA, Hermans SJ, Parker MW, Miles LA. Sci Rep 5 9649 (2015)
  3. Zhao J, Nussinov R, Ma B. MAbs 11 58-74 (2019)
  4. Zhao J, Nussinov R, Ma B. J Biol Chem 292 18325-18343 (2017)
  5. Hassan M, Shahzadi S, Seo SY, Alashwal H, Zaki N, Moustafa AA. Front Comput Neurosci 12 34 (2018)
  6. Bekker GJ, Fukuda I, Higo J, Kamiya N. Sci Rep 10 1406 (2020)
  7. Greene D, Po T, Pan J, Tabibian T, Luo R. J Phys Chem B 122 4521-4536 (2018)
  8. 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)
  9. Wang H, Yan X, Zhang Y, Wang P, Li J, Zhang X. J Alzheimers Dis Rep 8 101-128 (2024)


Reviews citing this publication (17)

  1. Chen GF, Xu TH, Yan Y, Zhou YR, Jiang Y, Melcher K, Xu HE. Acta Pharmacol Sin 38 1205-1235 (2017)
  2. 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. van Dyck CH. Biol Psychiatry 83 311-319 (2018)
  4. Rajasekhar K, Govindaraju T. RSC Adv 8 23780-23804 (2018)
  5. Schilling S, Rahfeld JU, Lues I, Lemere CA. Molecules 23 E1068 (2018)
  6. Kulkarni P, Solomon TL, He Y, Chen Y, Bryan PN, Orban J. Protein Sci 27 1557-1567 (2018)
  7. Montoliu-Gaya L, Villegas S. Expert Rev Mol Med 18 e13 (2016)
  8. Vander Zanden CM, Chi EY. J Pharm Sci 109 68-73 (2020)
  9. Sumner IL, Edwards RA, Asuni AA, Teeling JL. Front Neurosci 12 254 (2018)
  10. Morató X, Pytel V, Jofresa S, Ruiz A, Boada M. Int J Mol Sci 23 9305 (2022)
  11. Rinauro DJ, Chiti F, Vendruscolo M, Limbocker R. Mol Neurodegener 19 20 (2024)
  12. Boopathi S, Poma AB, Garduño-Juárez R. Int J Mol Sci 22 10798 (2021)
  13. Hunter S, Smailagic N, Brayne C. Eur J Clin Invest 48 e13025 (2018)
  14. Decourt B, Noorda K, Noorda K, Shi J, Sabbagh MN. J Exp Pharmacol 14 331-352 (2022)
  15. Agrawal N, Skelton AA. Protein J 38 425-434 (2019)
  16. Pandey G, Ramakrishnan V. Biophys Rev 12 1175-1186 (2020)
  17. Bilodeau PA, Dickson JR, Kozberg MG. J Clin Med 13 1245 (2024)

Articles citing this publication (23)

  1. 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. 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. Bouter Y, Lopez Noguerola JS, Tucholla P, Crespi GA, Parker MW, Wiltfang J, Miles LA, Bayer TA. Acta Neuropathol 130 713-729 (2015)
  4. 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. Bellucci L, Ardèvol A, Parrinello M, Lutz H, Lu H, Weidner T, Corni S. Nanoscale 8 8737-8748 (2016)
  6. 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. Rauth S, Hinz D, Börger M, Uhrig M, Mayhaus M, Riemenschneider M, Skerra A. Biochem J 473 1563-1578 (2016)
  8. Bellucci L, Bussi G, Di Felice R, Corni S. Nanoscale 9 2279-2290 (2017)
  9. 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)
  10. Rofo F, Metzendorf NG, Saubi C, Suominen L, Godec A, Sehlin D, Syvänen S, Hultqvist G. Alzheimers Res Ther 14 180 (2022)
  11. Bekker GJ, Kamiya N. Methods Mol Biol 2266 187-202 (2021)
  12. 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)
  13. 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)
  14. Zhang T, Zhang T, Nagel-Steger L, Willbold D. ChemistryOpen 8 989-994 (2019)
  15. Readel ER, Patel A, Putman JI, Du S, Armstrong DW. Sci Rep 13 12387 (2023)
  16. Romei MG, Leonard B, Kim I, Kim HS, Lazar GA. J Biol Chem 299 104685 (2023)
  17. Published Erratum Hunter S, Brayne C. J Negat Results Biomed 16 8 (2017)
  18. Hunter S, Brayne C. Aging Brain 1 100008 (2021)
  19. Firouzi R, Sowlati-Hashjin S, Chávez-García C, Ashouri M, Karimi-Jafari MH, Karttunen M. Int J Mol Sci 24 8161 (2023)
  20. Zott B, Nästle L, Grienberger C, Unger F, Knauer MM, Wolf C, Keskin-Dargin A, Feuerbach A, Busche MA, Skerra A, Konnerth A. Nat Commun 15 5819 (2024)
  21. Leite JP, Gales L. FEBS Lett 593 128-137 (2019)
  22. Bhattacharya S, Xu L, Thompson D. Methods Mol Biol 2340 401-448 (2022)
  23. Posado-Fernández A, Afonso CF, Dória G, Flores O, Cabrita EJ. Sci Rep 9 12241 (2019)


Quick links