Cited by 11Ion Transport and Channel RegulationMultiple Sclerosis Research StudiesEnzyme Structure and Function

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Structural basis of aquaporin-4 autoantibody binding in neuromyelitis optica

Open access
Gupta, Meghna, Khandelwal, Nitesh Kumar, Nelson, Andrew, Hwang, Peter, Pourmal, Sergei, Bennett, Jeffrey L., Stroud, Robert M.·2025·Science Advances

Published version of a preprint

Abstract

Neuromyelitis optica (NMO) is an autoimmune disease of the central nervous system where pathogenic autoantibodies target the water channel aquaporin-4 on human astrocytes causing neurological impairment. Autoantibody binding leads to complement-dependent and complement-independent cytotoxicity, ultimately resulting in astrocyte death, demyelination, and neuronal loss. Aquaporin-4 assembles in astrocyte plasma membranes as symmetric tetramers or as arrays of tetramers. We report molecular structures of aquaporin-4 alone and bound to Fab fragments from patient-derived NMO autoantibodies using cryogenic electron microscopy. Each antibody binds to epitopes comprised of three extracellular loops of aquaporin-4 with contributions from multiple molecules in the assembly. The structures distinguish between antibodies that bind to the tetrameric form of aquaporin-4 and those targeting higher-order orthogonal arrays of tetramers that provide more diverse bridging epitopes.

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Research works printed but not linked: 34

  1. 10.1038/s41572-020-0214-9 · DOI
  2. 10.1097/WNO.0000000000000508 · DOI
  3. 10.1007/s00401-013-1220-8 · DOI
  4. 10.1002/ana.24630 · DOI
  5. 10.1002/ana.21802 · DOI
  6. 10.1007/s00401-013-1172-z · DOI
  7. 10.1093/brain/awac079 · DOI
  8. 10.1172/JCI122942 · DOI
  9. 10.1016/S1474-4422(20)30392-6 · DOI
  10. 10.1242/jcs.042341 · DOI
  11. 10.1074/jbc.M110.123000 · DOI
  12. 10.1074/jbc.M115.647149 · DOI
  13. 10.1016/j.jneuroim.2011.05.001 · DOI
  14. 10.1073/pnas.0902725106 · DOI
  15. 10.1002/glia.20855 · DOI
  16. 10.1074/jbc.M111.227298 · DOI
  17. 10.1016/S0006-3495(93)81293-1 · DOI
  18. 10.1016/j.jmb.2005.10.081 · DOI
  19. 10.1073/pnas.1012867108 · DOI
  20. 10.1523/JNEUROSCI.1987-15.2015 · DOI
  21. 10.1002/glia.23231 · DOI
  22. 10.1002/jnr.22822 · DOI
  23. 10.1002/glia.22417 · DOI
  24. 10.1073/pnas.1109980108 · DOI
  25. 10.1016/j.jmb.2007.05.022 · DOI
  26. P. L. Chiu J. D. Orjuela B. L. de Groot C. Aponte-Santamaria T. Walz Structure and dynamics of cholesterol-mediated aquaporin-0 arrays and implications for lipid rafts. bioRxiv 2023.05.16.540959 (2023); https://www.biorxiv.org/content/10.1101/2023.05.16.540959v3. · DOI
  27. 10.1038/nature04321 · DOI
  28. 10.1073/pnas.0405274101 · DOI
  29. 10.3389/fcell.2022.866980 · DOI
  30. 10.1002/glia.22635 · DOI
  31. 10.1016/j.bpj.2017.03.012 · DOI
  32. 10.1096/fj.11-201608 · DOI
  33. 10.1038/nmeth.4169 · DOI · Paper page
  34. 10.7554/eLife.01456 · DOI

Metadata

Authors
Gupta, M., Khandelwal, N. K., Nelson, A., Hwang, P., Pourmal, S., Bennett, J. L., & Stroud, R. M.
Affiliations
  • Oregon Health & Science University (US)
  • University of California, San Francisco (US)
  • University of Colorado Anschutz (US)
Corresponding author
  • Gupta, Meghna
  • Bennett, Jeffrey L.
  • Stroud, Robert M.
Venue
Science Advances
Published
2025-02-21
Volume
11
Issue
8
Pages
eadq7560-eadq7560
ISSN
2375-2548 (ISSN-L)
OpenAlex
W4407802849
Cited by
11
References
1
Citations by year
2026: 6 · 2025: 4
FWCI
2.99
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Science Advances (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by-nd)
Funders
  • National Institutes of Health (1s10od026881-01, 1s10od021741-01, 1s10od020054-01)
  • National Institute on Aging (K99AG070271)
  • National Eye Institute (R01EY022936)
  • National Institute of General Medical Sciences (R01GM024485, R35GM156263, T32GM145460)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
  • Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
Keywords
neuromyelitis optica, aquaporin-4, autoantibodies, antibody-antigen binding, astrocytes, aquaporins, tetramer assembly, extracellular loop, antigenic determinants, cryo-EM structure, demyelination, complement-dependent cytotoxicity

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