Insight into inherited anemia CDA-I: disease-associated mutations disrupt Codanin1-CDIN1 complex
| Autoři | |
|---|---|
| Rok publikování | 2024 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Congenital dyserythropoietic anemias (CDAs) are characterized by ineffective erythropoiesis and morphological abnormalities in erythrocytes and erythroblasts. One of them, CDA type I (CDAI), is rare hereditary anemia described by congenital abnormalities like interchromatin bridges and Swisscheeselike heterochromatin. CDAI 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 iondependent restriction endonuclease. Despite their undeniable importance for CDACDIN1 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 employed biophysical techniques to characterize the homo and heterodimerization of these proteins, along with their structural features. Additionally, we quantified CDIN1Codanin1 binding affinity in the low nanomolar range. Finally, we mapped the specific interaction regions on both proteins and demonstrated that diseaseassociated mutations within these regions disrupt the CDIN1Codanin1 complex formation. These findings represent a significant step forward in elucidating the molecular mechanisms underlying CDAI activation and progression. This knowledge holds promise for the future development of targeted therapies for this rare disease. |
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