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Cited by 557Hippo pathway signaling and YAP/TAZProtein Structure and DynamicsProtein Kinase Regulation and GTPase Signaling

The WW domain of Yes-associated protein binds a proline-rich ligand that differs from the consensus established for Src homology 3-binding modules.

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Chen, H I, Sudol, M·1995·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.92.17.7819PMC PMC41237
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Abstract

The WW domain has previously been described as a motif of 38 semiconserved residues found in seemingly unrelated proteins, such as dystrophin, Yes-associated protein (YAP), and two transcriptional regulators, Rsp-5 and FE65. The molecular function of the WW domain has been unknown until this time. Using a functional screen of a cDNA expression library, we have identified two putative ligands of the WW domain of YAP, which we named WBP-1 and WBP-2. Peptide sequence comparison between the two partial clones revealed a homologous region consisting of a proline-rich domain followed by a tyrosine residue (with the shared sequence PPPPY), which we shall call the PY motif. Binding assays and site-specific mutagenesis have shown that the PY motif binds with relatively high affinity and specificity to the WW domain of YAP, with the preliminary consensus XPPXY being critical for binding. Herein, we have implicated the WW domain with a role in mediating protein-protein interactions, as a variant of the paradigm set by Src homology 3 domains and their proline-rich ligands.

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  • WW domains bind to proteins containing a minimal consensus sequence of XPPXY.

    “WW domains are small modules of 35 to 40 amino acids that are characterized by four well conserved aromatic residues of which two are tryptophans, that bind to proteins containing a minimal consensus sequence of XPPXY (Bork and Sudol, 1994; Chen and Sudol, 1995).”

    From LRAD3, A Novel Low-Density Lipoprotein Receptor Family Member That Modulates Amyloid Precursor Protein Trafficking (2011) · cites this paper as Chen and Sudol, 1995

    The Abstract reports that the WW domain of YAP binds ligands with a PY motif and that a preliminary XPPXY consensus is critical for binding. The claim extends that result from YAP’s WW domain to WW domains generally and omits the preliminary qualification. (LLM, conf=0.85)

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Research works printed but not linked: 38

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Cited by

Sorted by citations

Authors
Chen, H. I., & Sudol, M.
Affiliations
Rockefeller University (US)
ORCID
Sudol, M
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1995-08-15
Volume
92
Issue
17
Pages
7819-7823
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.92.17.7819
PMC
PMC41237
OpenAlex
W2033152875
Cited by
557
References
0
Citations by year
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FWCI
10.28
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5k04ca001605-02)
  • National Cancer Institute (CA 01605)
  • National Institute of General Medical Sciences (5T32GM07739-16, T32GM007739)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
WW domain, YAP, PY motif, protein-protein interaction, Src homology 3 domain, ligand identification
MeSH terms
YAP-Signaling Proteins, Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Carrier Proteins, Cerebellum, Cloning, Molecular, Female, Glutathione Transferase, Humans, Lung, Molecular Sequence Data, Oligodeoxyribonucleotides, Ovary, Phosphoproteins, Proline, Recombinant Fusion Proteins, Transcription Factors, Restriction Mapping, Gene Library, Polymerase Chain Reaction, Open Reading Frames, Consensus Sequence, Conserved Sequence, Sequence Homology, Amino Acid, DNA Primers, DNA, Complementary, Muscle, Skeletal, Adaptor Proteins, Signal Transducing, Rats

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