| First Author | Watanabe-Matsui M | Year | 2015 |
| Journal | Arch Biochem Biophys | Volume | 565 |
| Pages | 25-31 | PubMed ID | 25444856 |
| Mgi Jnum | J:326241 | Mgi Id | MGI:7310017 |
| Doi | 10.1016/j.abb.2014.11.005 | Citation | Watanabe-Matsui M, et al. (2015) Heme binds to an intrinsically disordered region of Bach2 and alters its conformation. Arch Biochem Biophys 565:25-31 |
| abstractText | The transcriptional repressor Bach2 regulates humoral and cellular immunity, including antibody class switching. It possesses a basic leucine zipper domain that mediates DNA binding. Heme inhibits the DNA-binding activity of Bach2 in vitro and induces the degradation of Bach2 in B cells. However, the structural basis of the heme-Bach2 interaction has not been identified. Spectroscopic analyses revealed that Bach2(331-520) is the heme-binding domain, as it includes three Cys-Pro motifs known to be important for heme binding. Heme-titration experiments demonstrated the presence of 5- and 6-coordinated heme-binding modes. Circular dichroism measurements indicated that Bach2(331-520) exists mostly in a random-coil conformation. However, dynamic light scattering analyses showed that, upon heme binding to Bach2(331-520), this region becomes denatured at a lower temperature, as compared with unbound Bach2(331-520). In addition, small-angle X-ray scattering and chemical modification analyses revealed that heme binding induces conformational alterations within the unstructured region. A GAL4-based luciferase assay in 293T cells showed that heme alters the protein interactions mediated by Bach2(331-520). These observations suggested that the unstructured region of Bach2 is important for heme binding, and consequently for its functional regulation. |
