2GHP

Crystal structure of the N-terminal 3 RNA binding domains of the yeast splicing factor Prp24

Summary for 2GHP

• Entry DOI: 10.2210/pdb2ghp/pdb
• Descriptor: U4/U6 snRNA-associated splicing factor PRP24 (2 entities in total)
• Functional Keywords: rna chaperone, rna binding domain, rna recognition motif, splicing factor, snrnp, spliceosome, structural genomics, protein structure initiative, psi, center for eukaryotic structural genomics, cesg, rna binding protein
• Biological source: Saccharomyces cerevisiae (baker's yeast)
• Cellular location: Nucleus: P49960
• Total number of polymer chains: 8
• Total formula weight: 267210.87

Authors

Bae, E.,Wesenberg, G.E.,Phillips Jr., G.N.,Bitto, E.,Bingman, C.A.,Center for Eukaryotic Structural Genomics (CESG) (deposition date: 2006-03-27, release date: 2006-04-25, Last modification date: 2024-10-09)

Primary citation

Bae, E.,Reiter, N.J.,Bingman, C.A.,Kwan, S.S.,Lee, D.,Phillips Jr., G.N.,Butcher, S.E.,Brow, D.A.
Structure and interactions of the first three RNA recognition motifs of splicing factor prp24.
J.Mol.Biol., 367:1447-1458, 2007

PubMed Abstract: The essential Saccharomyces cerevisiae pre-messenger RNA splicing protein 24 (Prp24) has four RNA recognition motifs (RRMs) and facilitates U6 RNA base-pairing with U4 RNA during spliceosome assembly. Prp24 is a component of the free U6 small nuclear ribonucleoprotein particle (snRNP) but not the U4/U6 bi-snRNP, and so is thought to be displaced from U6 by U4/U6 base-pairing. The interaction partners of each of the four RRMs of Prp24 and how these interactions direct U4/U6 pairing are not known. Here we report the crystal structure of the first three RRMs and the solution structure of the first two RRMs of Prp24. Strikingly, RRM 2 forms extensive inter-domain contacts with RRMs 1 and 3. These contacts occupy much of the canonical RNA-binding faces (beta-sheets) of RRMs 1 and 2, but leave the beta-sheet of RRM 3 exposed. Previously identified substitutions in Prp24 that suppress mutations in U4 and U6 spliceosomal RNAs cluster primarily in the beta-sheet of RRM 3, but also in a conserved loop of RRM 2. RNA binding assays and chemical shift mapping indicate that a large basic patch evident on the surface of RRMs 1 and 2 is part of a high affinity U6 RNA binding site. Our results suggest that Prp24 binds free U6 RNA primarily with RRMs 1 and 2, which may remodel the U6 secondary structure. The beta-sheet of RRM 3 then influences U4/U6 pairing through interaction with an unidentified ligand.

PubMed: 17320109
DOI: 10.1016/j.jmb.2007.01.078

Experimental method

X-RAY DIFFRACTION (2.7 Å)