Formin Binding Proteins Bear WWP/WW Domains That Bind Proline-rich Peptides and Functionally Resemble SH3 Domains

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1996 Mar 1

PMID 8605874

Citations 60

Authors

D C Chan

M T Bedford

P Leder

Affiliations

Soon will be listed here.

Abstract

The formins, proteins involved in murine limb and kidney development, contain a proline-rich region that matches consensus sequences for Src homology 3 (SH3) ligands. To identify proteins that interact with formins, we used this proline-rich region to screen mouse limb bud expression libraries for formin binding proteins (FBPs). As expected, we found one class of FBPs that contains SH3 domains, including two novel members of this class. In addition, however, we also found a novel class of FBPs that contains one or two copies of a 26 amino acid homology region that has been recently termed the WWP or WW motif. We demonstrate that WWP/WW domains as short as 26 amino acids can act as modular protein-binding interfaces that bind with high affinity to proline-rich sequences that are similar and, in some cases, identical to SH3 ligands. Furthermore, we find that the WWP/WW domain can compete with the Abl SH3 domain in binding a proline-rich peptide present in formin. Our results suggest that these novel protein interaction domains can perform functions similar to those of SH3 domains and, thus, might regulate SH3 interactions with target proteins through competitive binding.

Citing Articles

PRPF40A induces inclusion of exons in GC-rich regions important for human myeloid cell differentiation.

Tan C, Sim D, Zhen Y, Tian H, Koh J, Roca X Nucleic Acids Res. 2024; 52(15):8800-8814.

PMID: 38943321 PMC: 11347146. DOI: 10.1093/nar/gkae557.

Intramolecular autoinhibition regulates the selectivity of PRPF40A tandem WW domains for proline-rich motifs.

Martinez-Lumbreras S, Trager L, Mulorz M, Payr M, Dikaya V, Hipp C Nat Commun. 2024; 15(1):3888.

PMID: 38719828 PMC: 11079029. DOI: 10.1038/s41467-024-48004-x.

Peripheral thickening of the sarcomeres and pointed end elongation of the thin filaments are both promoted by SALS and its formin interaction partners.

Farkas D, Szikora S, Jijumon A, Polgar T, Patai R, Toth M PLoS Genet. 2024; 20(1):e1011117.

PMID: 38198522 PMC: 10805286. DOI: 10.1371/journal.pgen.1011117.

Probing the ligand binding specificity of FNBP4 WW domains and interaction with FH1 domain of FMN1.

Das S, Maiti S Curr Res Struct Biol. 2024; 7:100119.

PMID: 38188541 PMC: 10770428. DOI: 10.1016/j.crstbi.2023.100119.

Bi-allelic loss-of-function variants in WBP4, encoding a spliceosome protein, result in a variable neurodevelopmental syndrome.

Engal E, Oja K, Maroofian R, Geminder O, Le T, Marzin P Am J Hum Genet. 2023; 110(12):2112-2119.

PMID: 37963460 PMC: 10716347. DOI: 10.1016/j.ajhg.2023.10.013.

References

Zhan X, Plourde C, Hu X, Friesel R, Maciag T . Association of fibroblast growth factor receptor-1 with c-Src correlates with association between c-Src and cortactin. J Biol Chem. 1994; 269(32):20221-4. View

Feng S, Chen J, Yu H, Simon J, Schreiber S . Two binding orientations for peptides to the Src SH3 domain: development of a general model for SH3-ligand interactions. Science. 1994; 266(5188):1241-7. DOI: 10.1126/science.7526465. View

Andre B, Springael J . WWP, a new amino acid motif present in single or multiple copies in various proteins including dystrophin and the SH3-binding Yes-associated protein YAP65. Biochem Biophys Res Commun. 1994; 205(2):1201-5. DOI: 10.1006/bbrc.1994.2793. View

COHEN G, Ren R, Baltimore D . Modular binding domains in signal transduction proteins. Cell. 1995; 80(2):237-48. DOI: 10.1016/0092-8674(95)90406-9. View

Bork P, Sudol M . The WW domain: a signalling site in dystrophin?. Trends Biochem Sci. 1994; 19(12):531-3. DOI: 10.1016/0968-0004(94)90053-1. View

Bork P, Margolis B . A phosphotyrosine interaction domain. Cell. 1995; 80(5):693-4. DOI: 10.1016/0092-8674(95)90347-x. View

Huibregtse J, Scheffner M, Beaudenon S, Howley P . A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proc Natl Acad Sci U S A. 1995; 92(7):2563-7. PMC: 42258. DOI: 10.1073/pnas.92.7.2563. View

Woychik R, Stewart T, Davis L, DEustachio P, Leder P . An inherited limb deformity created by insertional mutagenesis in a transgenic mouse. Nature. 1985; 318(6041):36-40. DOI: 10.1038/318036a0. View

Zeller R, Leder P . The limb deformity gene is required for apical ectodermal ridge differentiation and anteroposterior limb pattern formation. Genes Dev. 1989; 3(10):1481-92. DOI: 10.1101/gad.3.10.1481. View

10.

Woychik R, Maas R, Zeller R, Vogt T, Leder P . 'Formins': proteins deduced from the alternative transcripts of the limb deformity gene. Nature. 1990; 346(6287):850-3. DOI: 10.1038/346850a0. View

11.

Soriano P, Montgomery C, Geske R, Bradley A . Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell. 1991; 64(4):693-702. DOI: 10.1016/0092-8674(91)90499-o. View

12.

Schwartzberg P, Stall A, Hardin J, Bowdish K, Humaran T, Boast S . Mice homozygous for the ablm1 mutation show poor viability and depletion of selected B and T cell populations. Cell. 1991; 65(7):1165-75. DOI: 10.1016/0092-8674(91)90012-n. View

13.

Wu H, Reynolds A, Kanner S, Vines R, Parsons J . Identification and characterization of a novel cytoskeleton-associated pp60src substrate. Mol Cell Biol. 1991; 11(10):5113-24. PMC: 361526. DOI: 10.1128/mcb.11.10.5113-5124.1991. View

14.

Trumpp A, Blundell P, de la Pompa J, Zeller R . The chicken limb deformity gene encodes nuclear proteins expressed in specific cell types during morphogenesis. Genes Dev. 1992; 6(1):14-28. DOI: 10.1101/gad.6.1.14. View

15.

Kuo A, Leder P . A variant limb deformity transcript expressed in the embryonic mouse limb defines a novel formin. Genes Dev. 1992; 6(1):29-37. DOI: 10.1101/gad.6.1.29. View

16.

Sulston J, Du Z, Thomas K, Wilson R, Hillier L, Staden R . The C. elegans genome sequencing project: a beginning. Nature. 1992; 356(6364):37-41. DOI: 10.1038/356037a0. View

17.

Chenevert J, Corrado K, Bender A, Pringle J, Herskowitz I . A yeast gene (BEM1) necessary for cell polarization whose product contains two SH3 domains. Nature. 1992; 356(6364):77-9. DOI: 10.1038/356077a0. View

18.

Clark S, Stern M, Horvitz H . C. elegans cell-signalling gene sem-5 encodes a protein with SH2 and SH3 domains. Nature. 1992; 356(6367):340-4. DOI: 10.1038/356340a0. View

19.

Kaelin Jr W, Krek W, Sellers W, DeCaprio J, Ajchenbaum F, Fuchs C . Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties. Cell. 1992; 70(2):351-64. DOI: 10.1016/0092-8674(92)90108-o. View

20.

Lowenstein E, Daly R, Batzer A, Li W, Margolis B, Lammers R . The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell. 1992; 70(3):431-42. DOI: 10.1016/0092-8674(92)90167-b. View