4YH8: Structure Of Yeast U2af Complex

Citation:
Abstract
The pre-mRNA splicing reaction of eukaryotic cells has to be carried out extremely accurately, as failure to recognize the splice sites correctly causes serious disease. The small subunit of the U2AF heterodimer is essential for the determination of 3' splice sites in pre-mRNA splicing, and several single-residue mutations of the U2AF small subunit cause severe disorders such as myelodysplastic syndromes. However, the mechanism of RNA recognition is poorly understood. Here we solved the crystal structure of the U2AF small subunit (U2AF23) from fission yeast, consisting of an RNA recognition motif (RRM) domain flanked by two conserved CCCH-type zinc fingers (ZFs). The two ZFs are positioned side by side on the beta sheet of the RRM domain. Further mutational analysis revealed that the ZFs bind cooperatively to the target RNA sequence, but the RRM domain acts simply as a scaffold to organize the ZFs and does not itself contact the RNA directly. This completely novel and unexpected mode of RNA-binding mechanism by the U2AF small subunit sheds light on splicing errors caused by mutations of this highly conserved protein.
PDB ID: 4YH8Download
MMDB ID: 131692
PDB Deposition Date: 2015/2/27
Updated in MMDB: 2015/08
Experimental Method:
x-ray diffraction
Resolution: 1.7  Å
Source Organism:
Similar Structures:
Biological Unit for 4YH8: dimeric; determined by author and by software (PISA)
Molecular Components in 4YH8
Label Count Molecule
Proteins (2 molecules)
1
Splicing Factor U2af 23 KDA Subunit(Gene symbol: SPAP8A3.06)
Molecule annotation
1
Splicing Factor U2af 59 KDA Subunit(Gene symbol: prp2)
Molecule annotation
Chemicals (2 molecules)
1
2
* Click molecule labels to explore molecular sequence information.

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