Figure 8.

Model of ADAM10 sheddase activation. (A) Stimuli leading to elevation of intracellular calcium induce ANO6 scramblase activation and PS externalization from the inner to the outer cell membrane leaflet. Hyperactive ANO6 induces ADAM10-mediated shedding even in the absence of any stimulus. Cationic amino acid residues in the stalk region of ADAM10 might interact with the negatively charged PS-head group. ADAM10–PS interaction seems to be a prerequisite for induced shedding. (B) Ribbon representation of the X-ray structure of the extracellular region of ADAM10 (pdb accession code: 6BE6) (Seegar et al., 2017). Colour coding of the different domains is according to A and the Zn-ion in the catalytic centre is depicted in red. Cationic amino-acid residues in the stalk region responsible for the PS interaction are missing in the X-ray structure and are depicted in one-letter code.