6YVH

CWC22-CWC27-EIF4A3 Complex

Summary for 6YVH

• Entry DOI: 10.2210/pdb6yvh/pdb
• Descriptor: Pre-mRNA-splicing factor CWC22 homolog, Spliceosome-associated protein CWC27 homolog, Eukaryotic initiation factor 4A-III (3 entities in total)
• Functional Keywords: ejc helicase, rna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 12
• Total formula weight: 237977.42

Authors

Basquin, J.,Busetto, V.,LeHir, H.,Conti, E. (deposition date: 2020-04-28, release date: 2020-05-13, Last modification date: 2024-01-24)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.19 Å)