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          Institute: MPI für Entwicklungsbiologie     Collection: Abteilungsunabhängige Arbeitsgruppen     Display Documents

ID: 706599.0, MPI für Entwicklungsbiologie / Abteilungsunabhängige Arbeitsgruppen
Structural and functional framework for the autoinhibition of Nedd4-family ubiquitin ligases
Authors:Mari, S.; Ruetalo, N.; Maspero, E.; Stoffregen, M. C.; Pasqualato, S.; Polo, S.; Wiesner, S.
Date of Publication (YYYY-MM-DD):2014-11-04
Title of Journal:Structure
Journal Abbrev.:Structure
Issue / Number:11
Start Page:1639
End Page:1649
Sequence Number of Article:25438670
Review Status:Internal review
Audience:Experts Only
Abstract / Description:Nedd4-family ubiquitin ligases are key regulators of cell surface receptor signaling. Their dysregulation is associated with several human diseases, including cancer. Under normal conditions, the activity of various Nedd4 E3s is controlled through an autoinhibitory interaction of the N-terminal C2 domain with the C-terminal catalytic HECT domain. Here, we report the structural and functional framework for this intramolecular interaction. Our nuclear magnetic resonance (NMR) data and biochemical analyses on Smurf2 and Nedd4 show that the C2 domain has the potential to regulate E3 activity by maintaining the HECT domain in a low-activity state where its ability for transthiolation and noncovalent Ub binding are impaired.
External Publication Status:published
Document Type:Article
Affiliations:MPI für Entwicklungsbiologie/Abteilungsunabhängige Arbeitsgruppen/Arbeitsgruppe Wiesner
External Affiliations:Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tubingen, Germany. Crystallography Unit, Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, Milan 20139, Italy. IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Istituto Europeo di Oncologia, Via Adamello 16, Milan 20139, Italy; Dipartimento di Scienze della Salute, Universita' degli Studi di Milano, Via di Rudini 8, Milan 20122, Italy. Electronic address: simona.polo@ifom.eu. Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tubingen, Germany. Electronic address: silke.wiesner@tue.mpg.de.
Identifiers:ISSN:1878-4186 (Electronic) 0969-2126 (Linking) %R 10.1... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/25438670 [ID No:2]
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