| RRC ID |
90102
|
| 著者 |
Brolih S, Ali HS, Scott C, Olijnik AA, Aitkenhead H, Moir-Meyer G, Gavard AE, Yosaatmadja Y, Higgs DR, Buckle V, Roy N, Gileadi O, Newman JA, Duarte F, Babbs C, McHugh PJ.
|
| タイトル |
CDIN1-Codanin-1 complex defective in congenital dyserythropoietic anaemia type I is an RNA nuclease.
|
| ジャーナル |
Nat Commun
|
| Abstract |
Congenital Dyserythropoietic Anaemia type I (CDA-I) is a rare inherited disorder of erythropoiesis, in which erythroid cells display a unique nuclear phenotype referred to as 'spongy' heterochromatin. The molecular basis of CDA-I remains unknown, with most cases of CDA-I caused by mutations in CDAN1, encoding Codanin-1, or CDIN1, encoding for Codanin-1-interacting nuclease 1 (CDIN1). To date, very little is known about the function of CDA-I disease proteins and the mechanism by which their associated mutations cause disease. Here, we demonstrate that endogenous CDIN1 interacts with Codanin-1, to form a stable complex. Structural and functional analysis of this complex reveals that the CDIN1-Codanin-1 complex is an RNA nuclease. We shed light on the key mechanistic features of the complex using biochemical and biophysical approaches, complemented by all-atom molecular dynamics (MD) structural simulations. We identify various functional consequences of founder patient mutations on the RNA nuclease activity of CDIN1, providing a framework for understanding the pathophysiology and developing therapeutic strategies for CDA-I.
|
| 巻・号 |
17(1)
|
| 公開日 |
2026-7-2
|
| DOI |
10.1038/s41467-026-74766-7
|
| PII |
10.1038/s41467-026-74766-7
|
| PMID |
42393042
|
| PMC |
PMC13463051
|
| MeSH |
Anemia, Dyserythropoietic, Congenital* / genetics
Anemia, Dyserythropoietic, Congenital* / metabolism
Glycoproteins* / chemistry
Glycoproteins* / genetics
Glycoproteins* / metabolism
Humans
Molecular Dynamics Simulation
Mutation
Nuclear Proteins* / chemistry
Nuclear Proteins* / genetics
Nuclear Proteins* / metabolism
Protein Binding
|
| リソース情報 |
| ヒト・動物細胞 |
HUDEP-2(RCB4557) |
