Congenital dyserythropoietic anemia type I (CDA‐I) is a rare hereditary disease marked by ineffective erythropoiesis, a characteristic spongy heterochromatin structure in erythroblasts, and mutations in the genes CDAN1 and CDIN1 , which encode the proteins Codanin1 and CDIN1. Codanin1 regulates histone shuttling via the chaperone ASF1, yet the role of CDIN1 in CDA‐I pathology remains unclear. Notably, CDIN1 is known to interact directly with the C‐terminus of Codanin1. Although mutations in both genes are critical to the disease phenotype, their molecular‐level effects have not been fully elucidated. Here, we present a comprehensive structural and functional analysis of the CDIN1‐Codanin1 C‐terminus complex. Using complementary biophysical techniques, we show that CDIN1 and Codanin1 C‐terminus form a high‐affinity heterodimeric complex with equimolar stoichiometry. We further delineate the essential interacting regions of CDIN1 and Codanin1. We demonstrate that CDA‐I‐associated mutations in either protein disrupt the CDIN1‐Codanin1 interaction, suggesting a potential molecular mechanism underlying the disease.
Stojaspal et al. (Thu,) studied this question.