Insight into inherited anemia CDA-I: disease-associated mutations disrupt Codanin1-CDIN1 complex
| Authors | |
|---|---|
| Year of publication | 2023 |
| Type | Appeared in Conference without Proceedings |
| MU Faculty or unit | |
| Citation | |
| Description | Congenital dyserythropoietic anemias (CDAs) cause ineffective erythropoiesis and morphological anomalies in erythrocytes and erythroblasts. One of them, CDA type I (CDA-I), is rare hereditary anemia described by congenital abnormalities like interchromatin bridges and Swiss-cheese-like heterochromatin. CDA-I is associated with mutations in two different loci, CDAN1 and CDIN1. CDAN1, encoding Codanin1, is involved in nucleosome assembly and disassembly. CDIN1 is a recently discovered protein predicted to be a divalent metal ion-dependent restriction endonuclease. Despite their undeniable importance for CDA-I progression, both proteins and their mutual interaction are poorly described. Here, we present a pioneer study of the essential interaction between CDIN1 and Codanin1. Firstly, we characterized the biophysical properties of both proteins. We investigated their homodimerization and heterodimerization and their structural features. Additionally, we quantified CDIN1-Codanin1 binding affinity in the low nanomolar range. Finally, we defined CDIN1-Codanin1 interaction regions and showed that CDA-I-related mutations residing in identified interaction regions disturb the CDIN1 Codanin1 complex. The results of this project are an essential step toward unraveling the CDA-I activation and progression process that will be employed in the future design of biological therapy. |
| Related projects: |