2b7e
First FF domain of Prp40 Yeast Protein
Structural highlights
FunctionPRP40_YEAST Required for pre-spliceosome formation, which is the first step of pre-mRNA splicing. This protein is associated with snRNP U1. Two commitment complexes, CC1 and CC2, have been defined in yeast. CC1 is a basal complex dependent only on the 5' splice site. CC2 is a complex of lower mobility and is dependent on a branchpoint as well as a 5' splice site region. This protein is involved in CC2 formation where it binds to the branchpoint binding protein MSL5, bridging the U1 snRNP-associated 5' splice site and the MSL5-associated branch point 3' intron splice site.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe yeast splicing factor Prp40 (pre-mRNA processing protein 40) consists of a pair of WW domains followed by several FF domains. The region comprising the FF domains has been shown to associate with the 5' end of U1 small nuclear RNA and to interact directly with two proteins, the Clf1 (Crooked neck-like factor 1) and the phosphorylated repeats of the C-terminal domain of RNA polymerase II (CTD-RNAPII). In this work we reported the solution structure of the first FF domain of Prp40 and the identification of a novel ligand-binding site in FF domains. By using chemical shift assays, we found a binding site for the N-terminal crooked neck tetratricopeptide repeat of Clf1 that is distinct and structurally separate from the previously identified CTD-RNAPII binding pocket of the FBP11 (formin-binding protein 11) FF1 domain. No interaction, however, was observed between the Prp40 FF1 domain and three different peptides derived from the CTD-RNAPII protein. Indeed, the equivalent CTD-RNAPII-binding site in the Prp40 FF1 domain is predominantly negatively charged and thus unfavorable for an interaction with phosphorylated peptide sequences. Sequence alignments and phylogenetic tree reconstructions using the FF domains of three functionally related proteins, Prp40, FBP11, and CA150, revealed that Prp40 and FBP11 are not orthologous proteins and supported the different ligand specificities shown by their respective FF1 domains. Our results also revealed that not all FF domains in Prp40 are functionally equivalent. We proposed that at least two different interaction surfaces exist in FF domains that have evolved to recognize distinct binding motifs. The structure of Prp40 FF1 domain and its interaction with the crn-TPR1 motif of Clf1 gives a new insight into the binding mode of FF domains.,Gasch A, Wiesner S, Martin-Malpartida P, Ramirez-Espain X, Ruiz L, Macias MJ J Biol Chem. 2006 Jan 6;281(1):356-64. Epub 2005 Oct 27. PMID:16253993[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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