5W0H

Structure of U2AF65 (U2AF2) RRM2 at 1.11 Angstrom Resolution

Summary for 5W0H

• Entry DOI: 10.2210/pdb5w0h/pdb
• Related: 5W0G
• Descriptor: Splicing factor U2AF 65 kDa subunit (2 entities in total)
• Functional Keywords: rna splicing factor, rna recognition motif, polypyrimidine tract, rna binding protein, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus: P26368
• Total number of polymer chains: 1
• Total formula weight: 8966.24

Authors

Agrawal, A.A.,Jenkins, J.L.,Kielkopf, C.L. (deposition date: 2017-05-30, release date: 2018-04-11, Last modification date: 2023-10-04)

Primary citation

Glasser, E.,Agrawal, A.A.,Jenkins, J.L.,Kielkopf, C.L.
Cancer-Associated Mutations Mapped on High-Resolution Structures of the U2AF2 RNA Recognition Motifs.
Biochemistry, 56:4757-4761, 2017

PubMed Abstract: Acquired point mutations of pre-mRNA splicing factors recur among cancers, leukemias, and related neoplasms. Several studies have established that somatic mutations of a U2AF1 subunit, which normally recognizes 3' splice site junctions, recur among myelodysplastic syndromes. The U2AF2 splicing factor recognizes polypyrimidine signals that precede most 3' splice sites as a heterodimer with U2AF1. In contrast with those of the well-studied U2AF1 subunit, descriptions of cancer-relevant U2AF2 mutations and their structural relationships are lacking. Here, we survey databases of cancer-associated mutations and identify recurring missense mutations in the U2AF2 gene. We determine ultra-high-resolution structures of the U2AF2 RNA recognition motifs (RRM1 and RRM2) at 1.1 Å resolution and map the structural locations of the mutated U2AF2 residues. Comparison with prior, lower-resolution structures of the tandem U2AF2 RRMs in the RNA-bound and apo states reveals clusters of cancer-associated mutations at the U2AF2 RRM-RNA or apo-RRM1-RRM2 interfaces. Although the role of U2AF2 mutations in malignant transformation remains uncertain, our results show that cancer-associated mutations correlate with functionally important surfaces of the U2AF2 splicing factor.

PubMed: 28850223
DOI: 10.1021/acs.biochem.7b00551

Experimental method

X-RAY DIFFRACTION (1.11 Å)