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bioRxiv · 10.64898/2026.09.01.748654

Structural basis for tetraspanin-dependent surface export and adhesive function of integrin α3β1

Litzau, L.·Wren, E.·Kruse, A. C.·Blacklow, S. C.
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Abstract

Integrin 3{beta}1 (ITG3{beta}1) is a member of an integrin subfamily that binds to laminin proteins and promotes attachment of epithelial cells to the basement membrane. ITG3{beta}1 forms a complex with the tetraspanin CD151, and loss-of-function mutations in both ITG3 and CD151 cause epidermolysis bullosa, a severe skin blistering disease resulting from a defect in basement membrane attachment. Here, we report the cryoEM structure of an ITG3{beta}1 complex with CD151 and show that mutation of CD151 at the binding interface disrupts complex formation in cells. Strikingly, CRISPR-mediated knockout of CD151 leads to a variably penetrant ITG3{beta}1 surface export defect that is restored by re-expression of wild-type but not interface-mutated CD151. Together, these studies define the molecular basis for binding of CD151 to ITG3{beta}1, and show that CD151 promotes ITG3{beta}1 surface export, providing a biochemical explanation for the CD151 loss-of-function phenotype in epidermolysis bullosa.

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Litzau, L., Wren, E., Kruse, A. C., Blacklow, S. C.. 2026-09-03. Structural basis for tetraspanin-dependent surface export and adhesive function of integrin α3β1. https://doi.org/10.64898/2026.09.01.748654

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