Abstract
Congenital dyserythropoietic anemia type I (CDA-I) is a rare hereditary disease characterized by ineffective erythropoiesis and associated mutations in two proteins – Codanin1 and CDIN1. The primary role of Codanin1 is nucleosome assembly regulation through interaction with ASF1. The role of recently discovered CDIN1 remains unknown, but CDIN1 has been known to interact directly with the C-terminus of Codanin1. Despite the critical role of identified mutations in Codanin1 and CDIN1, the effects of CDA-I-related mutations at the molecular level have not been elucidated.
Here, we reconstruct the structural envelopes of CDIN1 and Codanin1, determine stoichiometry, define essential interacting regions, and quantify mutual affinity. We demonstrate that the anemia-associated mutations disturb CDIN1 and Codanin1 binding. Our findings present new insights into the structure of Codanin1 and CDIN1 and the functional effects of disease-associated mutations as the next step in unraveling the molecular etiology of CDA-I disease.
Highlights
Full-length CDIN1 preferentially forms dimers, Codanin1Cterm monomers
CDIN1 binds Codanin1Cterm in equimolar ratio with nanomolar affinity
Determined interacting regions of CDIN1 and Codanin1Cterm contain mutations associated with CDA-I disease
CDA-I-related mutations disrupt the binding of CDIN1 and Codanin1Cterm
Competing Interest Statement
The authors have declared no competing interest.
