Fig. 2
From: A novel NODAL variant in a young embolic stroke patient with visceral heterotaxy
Genetic analysis of NODAL variant. A Family tree of the patient. WT: wild-type (B) Sanger-sequencing validated c.1016 T > C variant in the patient and the father. C The scheme of NODAL protein. Nodal is post-translationally cleaved and forms mature active ligand (red). Met339 is located in the active ligand (arrow). D Met339 and nearby residues are conserved across species. Genome alignment was obtained from UCSC genome browser (http://genome.ucsc.edu). E Evaluation of protein structure of M394 (red) and other residues (blue) on the TGF-β domain, whose changes are reported to cause heterotaxy. Protein structures of homo-dimerized Nodal mature protein (gray) and CFC1-EGF domain of CFC1 (yellow) were modeled by Alphafold2. L, S and F (orange) in CFC1 represent the three residues reported to be essential for binding to Nodal in CFC1 of mouse Cripto [11]. The molecular structure was drawn by PyMOL (www.pymol.org). Amino acids reported to cause visceral heterotaxy including M339 cluster at the CFC1 and Nodal binding site