Solution Structure of the SGTA Dimerisation Domain and Investigation of Its Interactions with the Ubiquitin-Like Domains of BAG6 and UBL4A
| Autor: | Aline C. Simon, Pawel Leznicki, Peter Simpson, Santiago Martínez-Lumbreras, Lisa R. Hale, David S. Bishop, Arjun Thapaliya, John F. Darby, Ewelina M. Krysztofinska, Rivka L. Isaacson, Newran Sriskandarajah, Stephen High, Caterina Alfano, Maria R. Conte |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular Magnetic Resonance Spectroscopy Cell Membranes lcsh:Medicine Bioinformatics Biochemistry Protein structure Protein Interaction Mapping lcsh:Science RETICULUM-ASSOCIATED DEGRADATION Cellular Stress Responses CHAPERONE Multidisciplinary biology PROLIFERATION Multidisciplinary Sciences Solutions Tetratricopeptide Cell Processes Endoplasmic Reticulum Stress Response Science & Technology - Other Topics Cellular Structures and Organelles Research Article Protein Binding EXPRESSION General Science & Technology Protein domain ENDOPLASMIC-RETICULUM INSERTION Structural Characterization Research and Analysis Methods Binding Competitive Protein–protein interaction MD Multidisciplinary RETROTRANSLOCATION Animals Humans Protein Interactions Ubiquitins Science & Technology COMPLEX Binding Sites Ubiquitin Microscale thermophoresis lcsh:R Biology and Life Sciences Proteins Membrane Proteins MICROSCALE THERMOPHORESIS Computational Biology Isothermal titration calorimetry Cell Biology Chaperone Proteins Protein Structure Tertiary Transmembrane Proteins Protein-Protein Interactions Multiprotein Complexes Chaperone (protein) biology.protein Biophysics lcsh:Q Protein Multimerization Carrier Proteins ANCHORED MEMBRANE-PROTEINS Software Alpha helix Molecular Chaperones |
| Zdroj: | Darby, J F, Krysztofinska, E M, Simpson, P J, Simon, A C, Leznicki, P, Sriskandarajah, N, Bishop, D S, Hale, L R, Alfano, C, Conte, M R, Martínez-Lumbreras, S, Thapaliya, A, High, S & Isaacson, R L 2014, ' Solution Structure of the SGTA Dimerisation Domain and Investigation of Its Interactions with the Ubiquitin-Like Domains of BAG6 and UBL4A ', PLOS One, vol. 9, no. 11, e113281 . https://doi.org/10.1371/journal.pone.0113281 PLoS ONE, Vol 9, Iss 11, p e113281 (2014) PLoS ONE |
| Popis: | Background The BAG6 complex resides in the cytosol and acts as a sorting point to target diverse hydrophobic protein substrates along their appropriate paths, including proteasomal degradation and ER membrane insertion. Composed of a trimeric complex of BAG6, TRC35 and UBL4A, the BAG6 complex is closely associated with SGTA, a co-chaperone from which it can obtain hydrophobic substrates. Methodology and Principal Findings SGTA consists of an N-terminal dimerisation domain (SGTA_NT), a central tetratricopeptide repeat (TPR) domain, and a glutamine rich region towards the C-terminus. Here we solve a solution structure of the SGTA dimerisation domain and use biophysical techniques to investigate its interaction with two different UBL domains from the BAG6 complex. The SGTA_NT structure is a dimer with a tight hydrophobic interface connecting two sets of four alpha helices. Using a combination of NMR chemical shift perturbation, isothermal titration calorimetry (ITC) and microscale thermophoresis (MST) experiments we have biochemically characterised the interactions of SGTA with components of the BAG6 complex, the ubiquitin-like domain (UBL) containing proteins UBL4A and BAG6. We demonstrate that the UBL domains from UBL4A and BAG6 directly compete for binding to SGTA at the same site. Using a combination of structural and interaction data we have implemented the HADDOCK protein-protein interaction docking tool to generate models of the SGTA-UBL complexes. Significance This atomic level information contributes to our understanding of the way in which hydrophobic proteins have their fate decided by the collaboration between SGTA and the BAG6 complex. |
| Databáze: | OpenAIRE |
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