Structural Basis for APPTPPPLPP Peptide Recognition by the FBP11WW1 Domain

Pires, Juliana Rico; Parthier, C.; Aido-Machado, Rodolpho do; Wiedemann, Urs Achim; Otte, Livia; Böhm, Gerald; Rudolph, Rainer; Oschkinat, Hartmut

doi:10.1016/j.jmb.2005.02.056

Cited by 23 publications

(54 citation statements)

References 34 publications

(29 reference statements)

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“…The bipartite mode of the PP1 and PP3 moieties in Htt-PRR and the tandem WW domains in HYPA significantly enhance their binding affinity. The first WW domain of HYPA is well ordered (29,(35)(36)(37), whereas it may have a chaperoning effect on the folding of the secondary WW domain. Our results indicate that the two WW domains work as a unit to interact with Htt-PRR.…”

Section: Bipartite Interaction Between Prr Of Htt and 2ww Of Hypa-mentioning

confidence: 99%

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

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Section: Bipartite Interaction Between Prr Of Htt and 2ww Of Hypa-mentioning

confidence: 99%

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

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“…The structures of the individual FBP21 WW domains are very similar to those of previously solved WW domain structures, and the pairwise r.m.s.d. of the ␤-sheet backbone atoms to the solution structures of WW domains from scPrp40 (7), hsFBP11 (22), mmFBP28 (39) are between 1.0 and 1.6 Å.…”

Section: Ww Domains Mediate the Interaction Of Fbp21 Withmentioning

confidence: 99%

“…P1, P2, and P3 contain PGM/PPR motifs that were postulated to bind to the WW domain of group III. Other peptides, derived from leukocyte formin (P4, residues 541-549) (43), DIAPH3 (P5, residues 589 -598) (44), and the SIPP1-derived peptide P6 (see above) contain PPLP or PPP motifs that were previously reported to interact with WW domains of group II (21,22). The data presented in Table 2 and Table 3 indicates that both WW domains of FBP21 recognize the group III PPR/ PGM-binding motif.…”

mentioning

confidence: 94%

“…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%

“…5, D and E). The canonical XP groove formed by residues Trp-29/70, Ser-27/68, and Tyr-18/59 is highly conserved in most WW domains (22). The second groove, the XP2 groove, is formed by residues Val-8/49, Glu-9/50, Gly-10/51, Tyr-18/59, and Tyr-20/61.…”

mentioning

confidence: 99%

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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

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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...

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Development of QSAR‐Improved Statistical Potential for the Structure‐Based Analysis of ProteinPeptide Binding Affinities

Han

2013

Molecular Informatics

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Proteinpeptide interactions have recently been found to play an essential role in constructing intracellular signaling networks. Understanding the molecular mechanism of such interactions and identification of the interacting partners would be of great value for developing peptide therapeutics against many severe diseases such as cancer. In this study, we describe a structure-based, general-purpose strategy for fast and reliably predicting proteinpeptide binding affinities. This strategy combines unsupervised knowledge-based statistical potential derived from 505 interfacially diverse, non-redundant proteinpeptide complex structures and supervised quantitative structure-activity relationship (QSAR) modeling trained by 250 proteinpeptide interactions with known structure and affinity data. The built partial least squares (PLS) model is confirmed to have high stability and predictive power by using internal 5-fold cross-validation and rigorous Monte Carlo cross-validation (MCCV). The model is further employed to analyze two large groups of HLA- and SH3-binding peptides based upon computationally modeled structures. Satisfactorily, although the PLS model is originally trained with dissociation constants (Kd ) of proteinpeptide binding, it shows a good correlation with other two affinity qualities, i.e. SPOT signal intensities (BLU) and half maximal competitive concentrations (IC50 ). Furthermore, we perform systematic comparisons of our method with several widely used, representative affinity predictors, including molecular mechanics-based MM-PB/SA, knowledge-based DFIRE and docking score HADDOCK, on a small panel of elaborately selected proteinpeptide systems. It is demonstrated that (i) the QSAR-improved statistical potential exhibits a comparable predictive performance with but can work faster than these traditional methods, and (ii) the crystal structure-derived statistical potential also supports the modeled and solution structures of proteinpeptide complexes. We expect that this hybrid method can be exploited as a new scoring tool to facilitate, for example, peptide docking and virtual screening.

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Structural Basis for APPTPPPLPP Peptide Recognition by the FBP11WW1 Domain

Cited by 23 publications

References 34 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)

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

Development of QSAR‐Improved Statistical Potential for the Structure‐Based Analysis of ProteinPeptide Binding Affinities

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