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Cited by 16Advanced Electron Microscopy Techniques and ApplicationsConnexins and lens biologyLipid Membrane Structure and Behavior

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Structure of the lens MP20 mediated adhesive junction

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Nicolas, William J., Shiriaeva, Anna, Martynowycz, Michael W., Grey, Angus C., Ruma, Yasmeen N., Donaldson, Paul J., Gonen, Tamir·2025·Nature Communications
DOI 10.1038/s41467-025-57903-6PMC PMC11947226

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Abstract

Human lens fiber membrane intrinsic protein MP20 is the second most abundant membrane protein of the human eye lens. Despite decades of effort its structure and function remained elusive. Here, we determined the MicroED structure of full-length human MP20 in lipidic-cubic phase to a resolution of 3.5 Å. MP20 forms tetramers each of which contain 4 transmembrane α-helices that are packed against one another forming a helical bundle. We find that each MP20 tetramer formed adhesive interactions with an opposing tetramer in a head-to-head fashion. Investigation of MP20 localization in human lenses indicate that in young fiber cells MP20 is initially localized to the cytoplasm in differentiating fiber cells but upon fiber cell maturation is inserted into the plasma membrane, correlating with the restriction of the diffusion of extracellular tracers into the lens. Together these results suggest that MP20 forms lens thin junctions in vivo, confirming its role as a structural protein in the human eye lens essential for its optical transparency.

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Metadata

Authors
Nicolas, W. J., Shiriaeva, A., Martynowycz, M. W., Grey, A. C., Ruma, Y. N., Donaldson, P. J., & Gonen, T.
Affiliations
  • Howard Hughes Medical Institute (US)
  • University of California, Los Angeles (US)
  • University of Auckland (NZ)
Corresponding author
Gonen, Tamir
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2025-03-26
Volume
16
Issue
1
Pages
2977-2977
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-025-57903-6
PMC
PMC11947226
OpenAlex
W4408854158
Cited by
16
References
2
Citations by year
2026: 6 · 2025: 8
FWCI
5.04
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by-nc)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Howard Hughes Medical Institute (N/A)
  • U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (P41GM136508)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Keywords
lens fiber cells, helical bundle, lipidic cubic phase, fiber cell differentiation, plasma membrane insertion, lens transparency, membrane protein structure

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