
==== Front
bioRxiv
BIORXIV
bioRxiv
Cold Spring Harbor Laboratory

10.1101/2024.05.13.594022
preprint
1
Article
Structure of the lens MP20 mediated adhesive junction
Nicolas William J. http://orcid.org/0000-0001-5970-8626

Shiriaeva Anna http://orcid.org/0000-0002-4082-7884

Martynowycz Michael W. http://orcid.org/0000-0003-0055-230X

Grey Angus C http://orcid.org/0000-0002-1540-1080

Ruma Yasmeen http://orcid.org/0000-0002-9817-8477

Donaldson Paul J
Gonen Tamir http://orcid.org/0000-0002-9254-4069

13 5 2024
2024.05.13.594022http://biorxiv.org/lookup/doi/10.1101/2024.05.13.594022
nihpp-2024.05.13.594022.pdf
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. Both the N- and C-termini of MP20 are cytoplasmic. We found that each MP20 tetramer formed adhesive interactions with an opposing tetramer in a head-to-head fashion. These interactions were mediated by the extracellular loops of the protein. The dimensions of the MP20 adhesive junctions are consistent with the 11 nm thin lens junctions. Investigation of MP20 localization in human lenses indicated that in young fiber cells MP20 was stored intracellularly in vesicles and upon fiber cell maturation MP20 inserted into the plasma membrane and restricted the extracellular space. 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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pmc
