دورية أكاديمية
Structural and functional analysis of the YAP-binding domain of human TEAD2.
| العنوان: | Structural and functional analysis of the YAP-binding domain of human TEAD2. |
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| المؤلفون: | Tian W; Departmentsof Pharmacology and Biochemistry, The University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA., Yu J, Tomchick DR, Pan D, Luo X |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2010 Apr 20; Vol. 107 (16), pp. 7293-8. Date of Electronic Publication: 2010 Apr 05. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | DNA-Binding Proteins/*chemistry , Transcription Factors/*chemistry, Amino Acid Sequence ; Binding Sites ; Cytoplasm/metabolism ; DNA/chemistry ; Dimerization ; Humans ; Molecular Sequence Data ; Phosphorylation ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Sequence Homology, Amino Acid ; Signal Transduction ; Surface Properties ; TEA Domain Transcription Factors |
| مستخلص: | The Hippo pathway controls organ size and suppresses tumorigenesis in metazoans by blocking cell proliferation and promoting apoptosis. The TEAD1-4 proteins (which contain a DNA-binding domain but lack an activation domain) interact with YAP (which lacks a DNA-binding domain but contains an activation domain) to form functional heterodimeric transcription factors that activate proliferative and prosurvival gene expression programs. The Hippo pathway inhibits the YAP-TEAD hybrid transcription factors by phosphorylating and promoting cytoplasmic retention of YAP. Here we report the crystal structure of the YAP-binding domain (YBD) of human TEAD2. TEAD2 YBD adopts an immunoglobulin-like beta-sandwich fold with two extra helix-turn-helix inserts. NMR studies reveal that the TEAD-binding domain of YAP is natively unfolded and that TEAD binding causes localized conformational changes in YAP. In vitro binding and in vivo functional assays define an extensive conserved surface of TEAD2 YBD as the YAP-binding site. Therefore, our studies suggest that a short segment of YAP adopts an extended conformation and forms extensive contacts with a rigid surface of TEAD. Targeting a surface-exposed pocket of TEAD might be an effective strategy to disrupt the YAP-TEAD interaction and to reduce the oncogenic potential of YAP. |
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| معلومات مُعتمدة: | R01 EY015708 United States EY NEI NIH HHS; R01 GM085004 United States GM NIGMS NIH HHS; GM085004 United States GM NIGMS NIH HHS; EY015708 United States EY NEI NIH HHS |
| سلسلة جزيئية: | PDB 3L15 |
| المشرفين على المادة: | 0 (DNA-Binding Proteins) 0 (TEA Domain Transcription Factors) 0 (TEAD2 protein, human) 0 (Transcription Factors) 9007-49-2 (DNA) |
| تواريخ الأحداث: | Date Created: 20100407 Date Completed: 20100527 Latest Revision: 20211203 |
| رمز التحديث: | 20240829 |
| مُعرف محوري في PubMed: | PMC2867681 |
| DOI: | 10.1073/pnas.1000293107 |
| PMID: | 20368466 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1091-6490 |
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| DOI: | 10.1073/pnas.1000293107 |