6YVH

CWC22-CWC27-EIF4A3 Complex

6YVH の概要

• エントリーDOI: 10.2210/pdb6yvh/pdb
• 分子名称: Pre-mRNA-splicing factor CWC22 homolog, Spliceosome-associated protein CWC27 homolog, Eukaryotic initiation factor 4A-III (3 entities in total)
• 機能のキーワード: ejc helicase, rna binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 237977.42

構造登録者

Basquin, J.,Busetto, V.,LeHir, H.,Conti, E. (登録日: 2020-04-28, 公開日: 2020-05-13, 最終更新日: 2024-01-24)

主引用文献

Busetto, V.,Barbosa, I.,Basquin, J.,Marquenet, E.,Hocq, R.,Hennion, M.,Paternina, J.A.,Namane, A.,Conti, E.,Bensaude, O.,Le Hir, H.
Structural and functional insights into CWC27/CWC22 heterodimer linking the exon junction complex to spliceosomes.
Nucleic Acids Res., 48:5670-5683, 2020

PubMed Abstract: Human CWC27 is an uncharacterized splicing factor and mutations in its gene are linked to retinal degeneration and other developmental defects. We identify the splicing factor CWC22 as the major CWC27 partner. Both CWC27 and CWC22 are present in published Bact spliceosome structures, but no interacting domains are visible. Here, the structure of a CWC27/CWC22 heterodimer bound to the exon junction complex (EJC) core component eIF4A3 is solved at 3Å-resolution. According to spliceosomal structures, the EJC is recruited in the C complex, once CWC27 has left. Our 3D structure of the eIF4A3/CWC22/CWC27 complex is compatible with the Bact spliceosome structure but not with that of the C complex, where a CWC27 loop would clash with the EJC core subunit Y14. A CWC27/CWC22 building block might thus form an intermediate landing platform for eIF4A3 onto the Bact complex prior to its conversion into C complex. Knock-down of either CWC27 or CWC22 in immortalized retinal pigment epithelial cells affects numerous common genes, indicating that these proteins cooperate, targeting the same pathways. As the most up-regulated genes encode factors involved in inflammation, our findings suggest a possible link to the retinal degeneration associated with CWC27 deficiencies.

PubMed: 32329775
DOI: 10.1093/nar/gkaa267

実験手法

X-RAY DIFFRACTION (3.19 Å)