Formin binding proteins bear WWP/WW domains that bind proline-rich peptides and functionally resemble SH3 domains.
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.
Chan
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DC
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Bedford
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MT
Leder
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P
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D005121:Extremities / Q000196:embryology; D050556:Fatty Acid-Binding Proteins; D005326:Fetal Proteins / Q000378:metabolism*; D000080865:Formins; D020690:GTPase-Activating Proteins; D015723:Gene Library; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011392:Proline / Q000737:chemistry; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D016601:RNA-Binding Proteins; D017386:Sequence Homology, Amino Acid; D018909:src Homology Domains / Q000235:genetics
D002352:Carrier Proteins; D018076:DNA, Complementary; D050556:Fatty Acid-Binding Proteins; D005326:Fetal Proteins; C106410:Fnbp1 protein, mouse; C491403:Fnbp3 protein, mouse; D000080865:Formins; D020690:GTPase-Activating Proteins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D010455:Peptides; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins; C491402:Srgap2 protein, mouse; D011392:Proline; C494957:FYN protein, human; C494960:Fyn protein, mouse; D016315:Proto-Oncogene Proteins c-abl; D051076:Proto-Oncogene Proteins c-fyn