Fig. 1.

(A) Scheme representing the two alternative splice forms of human CD59, which lack the GPI-anchoring domain and have C-terminal domains. (B) The 3D structure of human CD59 is shown with the secondary structure elements labeled and the five-disulfide bonds displayed (yellow). The N-glycan at Asn18 is marked in red. (C) Predicted structure of human IRIS-1 (cyan) superimposed onto canonical CD59. The C-terminal region of IRIS-1 (the last 28 residues) is missing in the experimental template and predicted to have different conformations: a helical structure (in cyan) packing against the remaining part of the protein, a more open conformation (in purple), or the C-terminal sequence of IRIS-1 is disordered (in dark blue) but could adopt a helical conformation when in contact with other macromolecules. (D) Predicted structure of human IRIS-2 (blue) superimposed onto canonical CD59. The predicted longer loop of IRIS-2 is flexible (blue). One disulfide bond, equivalent to C64–C69 of canonical human CD59 is missing due to C-terminal amino acid changes in IRIS-2. (E) Expression of CD59 isoforms: IRIS-1, IRIS-2, and canonical CD59 in human pancreatic islets and liver, RNA level. RT-PCR, n = 3, biological repeats. (F) Expression of IRIS-1 and IRIS-2 (relative to glyceraldehyde 3-phosphate dehydrogenase (GAPDH)) in various human tissues was measured by RT-PCR, n = 3 technical repeats. (G) Staining with specific antibodies against IRIS-1 or IRIS-2 (red) in dispersed, primary human pancreatic islets, and colocalization with insulin granules . Nuclei stained with DAPI (blue). Results are representative for donor #317 and were repeated with human pancreatic islets from three different healthy donors.