Solution Structure and Ligand Recognition of the WW Domain Pair of the Yeast Splicing Factor Prp40

Wiesner, Silke; Stier, Günter; Sattler, Michael; Macias, María J.

doi:10.1016/s0022-2836(02)01145-2

Cited by 79 publications

(103 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The structure was refined very well by using only short-range restraints as NOEs, hydrogen bonds, and dihedral angles (supplemental Table S1). This structure is somehow similar to that of its yeast homologue Prp40 (26), which was elucidated based on residual dipolar coupling (RDC) restraints besides NOEs. Especially, the structure includes a rigid helical linker that is close to WW2, implying that the helix contributes to the chaperoning effect on the folding of WW2.…”

Section: Resultsmentioning

confidence: 77%

Interaction with Polyglutamine-expanded Huntingtin Alters Cellular Distribution and RNA Processing of Huntingtin Yeast Two-hybrid Protein A (HYPA)

Jiang

Xia

Yuan

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 77%

Interaction with Polyglutamine-expanded Huntingtin Alters Cellular Distribution and RNA Processing of Huntingtin Yeast Two-hybrid Protein A (HYPA)

Jiang

Xia

Yuan

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…WWOX is one of several proteins that contain a pair of WW domains separated by an approximately 10 amino-acid linker. In the yeast splicing factor Prp40, this arrangement leads to outward facing WW domains that bind to different proteins and bring them into juxtaposition (Wiesner et al, 2002). This suggests that WWOX may also act as a bridge between different proteins.…”

mentioning

confidence: 99%

FRA16D common chromosomal fragile site oxido-reductase (FOR/WWOX) protects against the effects of ionizing radiation in Drosophila

et al. 2005

View full text Add to dashboard Cite

“…Only two tandem WW structures have been reported (7,14), one of which represents the two tandem WW domains of yeast splicing factor Prp40 (7). The WW domains of the Prp40 have a defined interdomain orientation, whereas the tandem WW domains of the mammalian FBP21 are connected by a much more flexible linker.…”

Section: Discussionmentioning

confidence: 99%

“…FBP21 contains a matrin-type zinc finger and two group III WW domains ( Fig. 1) that are structurally related to those of the established splicing factors U1C and Prp40, respectively (6,7). The binding of FBP21 to splicing factors is mediated by its tandem WW domains, which represent interaction modules for proline-rich ligands (4,8,9).…”

mentioning

confidence: 99%

“…Little is currently known about the functional importance of the interdomain linker in proteins with multiple WW domains. Although a number of structures of individual WW domains have been solved (17)(18)(19)(20)(21)(22), only two structures of tandem WW domains, namely those of yeast Prp40 and Drosophila Su(dx), have been determined, and their structures are markedly different (7,14). So far, the relationship between the functional diversity and the structural organization of multiple WW domains remains poorly characterized.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Structure and Function of the Two Tandem WW Domains of the Pre-mRNA Splicing Factor FBP21 (Formin-binding Protein 21)

Huang

Beullens

Zhang

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

Human FBP21 (formin-binding protein 21) contains a matrin-type zinc finger and two tandem WW domains. It is a component of the spliceosomes and interacts with several established splicing factors. Here we demonstrate for the first time that FBP21 is an activator of pre-mRNA splicing in vivo and that its splicing activation function and interaction with the splicing factor SIPP1 (splicing factor that interacts with PQBP1 and PP1) are both mediated by the two tandem WW domains of group III. We determined the solution structure of the tandem WW domains of FBP21 and found that the WW domains recognize peptide ligands containing either group II (PPLP) or group III (PPR) motifs. The binding interfaces involve both the XP and XP2 grooves of the two WW domains. Significantly, the tandem WW domains of FBP21 are connected by a highly flexible region, enabling their simultaneous interaction with two proline-rich motifs of SIPP1. The strong interaction between SIPP1 and FBP21 can be explained by the conjugation of two low affinity interactions with the tandem WW domains. Our study provides a structural basis for understanding the molecular mechanism underlying the functional implication of FBP21 and the biological specificity of tandem WW domains.Gene expression in eukaryotic cells involves several steps, including transcription, mRNA processing, and export. Pre-mRNA splicing takes place in the spliceosome, a highly dynamic ribonucleoprotein particle that consists of five small nuclear RNAs and at least 150 proteins. Small nuclear ribonucleoproteins (snRNPs) 3 and numerous protein factors are essential for the formation of the active spliceosome (1, 2). In budding yeast, the splicing factor Prp40 participates in crossintron bridging by interacting with the branch point-binding protein (BBP) and the U5 snRNP component Prp8. Prp40 contacts the 5Ј splice site and interacts with BBP, bringing the 5Ј splice site and the branch point in spatial proximity. These interactions are believed to be conserved in mammals (3-5). FBP21 (formin-binding protein 21), the mammalian Prp40-like protein, colocalizes with splicing factors in nuclear storage sites for pre-mRNA splicing factors. In addition, FBP21 is a component of the mammalian spliceosomal A/B complex and is associated with U2 snRNPs (6). FBP21 interacts directly with the splicing factors U1 snRNP protein U1C, the core snRNP proteins SmB and SmBЈ, and the branch point-binding protein SF1/mBBP, suggesting that it may also play a role in crossintron bridging of U1 and U2 snRNPs in the spliceosomes. FBP21 contains a matrin-type zinc finger and two group III WW domains ( Fig. 1) that are structurally related to those of the established splicing factors U1C and Prp40, respectively (6, 7). The binding of FBP21 to splicing factors is mediated by its tandem WW domains, which represent interaction modules for proline-rich ligands (4, 8, 9). Although the above data strongly suggest that FBP21 has a role in pre-mRNA splicing, there are no in vivo data to support this contention. The splicing...

show abstract

Solution Structure and Ligand Recognition of the WW Domain Pair of the Yeast Splicing Factor Prp40

Cited by 79 publications

References 56 publications

Interaction with Polyglutamine-expanded Huntingtin Alters Cellular Distribution and RNA Processing of Huntingtin Yeast Two-hybrid Protein A (HYPA)

Interaction with Polyglutamine-expanded Huntingtin Alters Cellular Distribution and RNA Processing of Huntingtin Yeast Two-hybrid Protein A (HYPA)

FRA16D common chromosomal fragile site oxido-reductase (FOR/WWOX) protects against the effects of ionizing radiation in Drosophila

Structure and Function of the Two Tandem WW Domains of the Pre-mRNA Splicing Factor FBP21 (Formin-binding Protein 21)

Contact Info

Product

Resources

About