Inherited anemia-associated mutations disrupt Codanin1 and CDIN1 mutual direct binding

ABSTRACT: Congenital dyserythropoietic anemia type I (CDA-I) is a rare hereditary disease that causes ineffective erythropoiesis and morphological abnormalities in bone marrow erythroblasts. The congenital abnormalities are manifested by internuclear bridges and Swiss-cheese-like heterochromatin. CDA-I is associated with mutations in two proteins, Codanin1 and CDIN1. Codanin1 is involved in nucleosome assembly and disassembly. CDIN1 is a recently discovered protein with a predicted structure similar to an endonuclease. The critical importance of Codanin1 and CDIN1 for CDA-I progression merited a thorough investigation of the structure-function relations of both proteins. Here, we reveal essential interacting regions between CDIN1 and Codanin1. We described the structural envelopes and the stoichiometry of proteins. Additionally, we quantified CDIN1-Codanin1 binding affinity in the low nanomolar range. Finally, we show how the anemia-associated mutations residing in defined interaction regions disturb the direct interaction of CDIN1 and Codanin1. The presented pivotal study of the structure and function of Codanin1 and CDIN1 is a significant step toward unraveling the CDA-I activation and progression mechanisms at the molecular level.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell

DISEASE(S): Acute Leukemia

SUBMITTER: Lenka Hernychova  

LAB HEAD: doc. Mgr. Ctirad Hofr, Ph.D.

PROVIDER: PXD037661 | Pride | 2026-09-07

REPOSITORIES: Pride