2HZC

Crystal structure of the N-terminal RRM of the U2AF large subunit

Replaces:  2FZR

Summary for 2HZC

• Entry DOI: 10.2210/pdb2hzc/pdb
• Related: 2G4B
• Descriptor: Splicing factor U2AF 65 kDa subunit, ZINC ION, HEXAETHYLENE GLYCOL, ... (4 entities in total)
• Functional Keywords: rna splicing, rrm, rna recognition, alternative conformation, rna binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P26368
• Total number of polymer chains: 1
• Total formula weight: 10043.14

Authors

Thickman, K.R.,Sickmier, E.A.,Kielkopf, C.L. (deposition date: 2006-08-08, release date: 2006-08-29, Last modification date: 2024-02-21)

Primary citation

Thickman, K.R.,Sickmier, E.A.,Kielkopf, C.L.
Alternative Conformations at the RNA-binding Surface of the N-terminal U2AF(65) RNA Recognition Motif.
J.Mol.Biol., 366:703-710, 2007

PubMed Abstract: The essential pre-mRNA splicing factor, U2 auxiliary factor 65KD (U2AF(65)) recognizes the polypyrimidine tract (Py-tract) consensus sequence of the pre-mRNA using two RNA recognition motifs (RRMs), the most prevalent class of eukaryotic RNA-binding domain. The Py-tracts of higher eukaryotic pre-mRNAs are often interrupted with purines, yet U2AF(65) must identify these degenerate Py-tracts for accurate pre-mRNA splicing. Previously, the structure of a U2AF(65) variant in complex with poly(U) RNA suggested that rearrangement of flexible side-chains or bound water molecules may contribute to degenerate Py-tract recognition by U2AF(65). Here, the X-ray structure of the N-terminal RRM domain of U2AF(65) (RRM1) is described at 1.47 A resolution in the absence of RNA. Notably, RNA-binding by U2AF(65) selectively stabilizes pre-existing alternative conformations of three side-chains located at the RNA interface (Arg150, Lys225, and Arg227). Additionally, a flexible loop connecting the beta2/beta3 strands undergoes a conformational change to interact with the RNA. These pre-existing alternative conformations may contribute to the ability of U2AF(65) to recognize a variety of Py-tract sequences. This rare, high-resolution view of an important member of the RRM class of RNA-binding domains highlights the role of alternative side-chain conformations in RNA recognition.

PubMed: 17188295
DOI: 10.1016/j.jmb.2006.11.077

Experimental method

X-RAY DIFFRACTION (1.47 Å)