| Pellino proteins contain a cryptic FHA domain that mediates interaction with phosphorylated IRAK1. | |
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MedLine Citation:
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PMID: 19081057 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pellino proteins are RING E3 ubiquitin ligases involved in signaling events downstream of the Toll and interleukin-1 (IL-1) receptors, key initiators of innate immune and inflammatory responses. Pellino proteins associate with and ubiquitinate proteins in these pathways, including the interleukin-1 receptor associated kinase-1 (IRAK1). We determined the X-ray crystal structure of a Pellino2 fragment lacking only the RING domain. This structure reveals that the IRAK1-binding region of Pellino proteins consists largely of a previously unidentified forkhead-associated (FHA) domain. FHA domains are well-characterized phosphothreonine-binding modules, and this cryptic example in Pellino2 can drive interaction of this protein with phosphorylated IRAK1. The Pellino FHA domain is decorated with an unusual appendage or "wing" composed of two long inserts that lie within the FHA homology region. Delineating how this E3 ligase associates with substrates, and how these interactions are regulated by phosphorylation, is crucial for a complete understanding of Toll/IL-1 receptor signaling. |
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Authors:
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Chun-Chi Lin; Yu-San Huoh; Karl R Schmitz; Liselotte E Jensen; Kathryn M Ferguson |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Structure (London, England : 1993) Volume: 16 ISSN: 0969-2126 ISO Abbreviation: Structure Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-12-16 Completed Date: 2009-02-20 Revised Date: 2012-06-27 |
Medline Journal Info:
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Nlm Unique ID: 101087697 Medline TA: Structure Country: United States |
Other Details:
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Languages: eng Pagination: 1806-16 Citation Subset: IM |
Affiliation:
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Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Motifs Amino Acid Sequence Binding Sites Cell Line Crystallography, X-Ray Escherichia coli / genetics Glutathione Transferase / metabolism Interleukin-1 Receptor-Associated Kinases / metabolism* Kidney / cytology Models, Chemical Models, Molecular Molecular Sequence Data Phosphorylation Phosphothreonine / metabolism Protein Binding Protein Structure, Secondary Protein Structure, Tertiary Proteins / chemistry*, genetics, isolation & purification, metabolism* Recombinant Fusion Proteins / chemistry, metabolism Sequence Homology, Amino Acid Substrate Specificity Ubiquitin-Protein Ligases / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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Y1-CO-1020/CO/NCI NIH HHS; Y1-GM-1104/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Proteins; 0/Recombinant Fusion Proteins; 1114-81-4/Phosphothreonine; EC 2.5.1.18/Glutathione Transferase; EC 2.7.11.1/IRAK1 protein, human; EC 2.7.11.1/Interleukin-1 Receptor-Associated Kinases; EC 6.3.2.19/Ubiquitin-Protein Ligases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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