8.A.77.1.4
Adam10 of 748 aas and 2 TMSs, an N- and a C-terminal TMS (Prox et al. 2012).  Both ADAM10 and ADAM17 shed CD16b (Guo et al. 2012) and CD23 (Mathews et al. 2010).  By destroying cell-cell contacts through cleavage of cadherins, the metalloproteinase ADAM10 (a disintegrin and metalloproteinase 10) critically contributes to α-toxin-dependent pathology of experimental S. aureus infections in mice. ADAM10 is a receptor for α-toxin (von Hoven et al. 2016; Virreira Winter et al. 2016). ADAM10 is docked to junctions by its transmembrane partner Tspan33, whose cytoplasmic C-terminus binds to the WW domain of PLEKHA7 in the presence of PDZD11. ADAM10 is locked at junctions through binding of its cytoplasmic C-terminus to afadin. Junctionally clustered ADAM10 supports the efficient formation of stable toxin pores. Instead, disruption of the PLEKHA7-PDZD11 complex inhibits ADAM10 and toxin junctional clustering. This promotes toxin pore removal from the cell surface through an actin- and macropinocytosis-dependent process, resulting in cell recovery from initial injury and survival (Shah et al. 2018). Shear stress activates ADAM10 sheddase to regulate Notch1 via the Piezo1 force sensor in endothelial cells (Caolo et al. 2020).  How the function of ADAM10 is regulated by tetraspanins, and how ADAM10 may promote enamel formation has been discussed (Shahid et al. 2022). Apoptosis-mediated ADAM10 activation removes a mucin barrier promoting T cell efferocytosis (Drexhage et al. 2024).  Regulation of ADAM10 activity may occur through microdomain-dependent intracellular calcium changes (Gharzia et al. 2024). At pH 7.5, both protomers in the dimer adopt an outward-facing (OF) conformation, with Zn²⁺ ions coordinated at the TMD binding site by distinct compositions. At pH 6.0, ZnT1 complexed with Zn²⁺ exhibits various conformations [OF/OF, OF/IF (inward-facing), and IF/IF] (Long et al. 2024).

---