{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies focused on the heme‐binding protein SOUL have revealed its unique biochemical and structural properties. Initially characterized in the retina and pineal gland, SOUL binds heme with high affinity and undergoes a distinct oligomeric transition—from a dimer in the apo‐form to a hexamer upon heme binding—exhibiting a 6‐coordinate low-spin heme configuration. Notably, the binding involves a critical histidine residue (His42), whose mutation abolishes heme affinity, suggesting that SOUL’s structure facilitates specific axial heme coordination that sets it apart from related proteins such as p22HBP."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther insights into SOUL’s function emerged from investigations into its protein–protein interactions. The heme-binding protein interacts with apoptosis-linked gene 2 (ALG-2) in a Ca2+-dependent manner, forming a 1:1 complex characterized by a significant conformational change and a large negative heat capacity change during binding. Mutagenesis studies pinpointed crucial residues (such as Phe100 in SOUL and Trp57 in ALG-2) essential for proper interaction dynamics. These findings suggest that through its ability to bind heme and engage in regulated interactions with proteins like ALG-2, SOUL may play a role in modulating cellular responses, potentially linking heme metabolism to pathways involved in Ca2+-mediated signal transduction and apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Emiko Sato, Ikuko Sagami, Takeshi Uchida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SOUL in mouse eyes is a new hexameric heme-binding protein with characteristic optical absorption, resonance Raman spectral, and heme-binding properties."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi048742i"}], "href": "https://doi.org/10.1021/bi048742i"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15518569"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15518569"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Taisuke Mikasa, Masami Kugo, Seigo Nishimura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thermodynamic Characterization of the Ca"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "2+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "-Dependent Interaction Between SOUL and ALG-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms19123802"}], "href": "https://doi.org/10.3390/ijms19123802"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30501057"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30501057"}]}]}]}