| Title: | The RING domain of the scaffold protein Ste5 adopts a molten globular character with high thermal and chemical stability |
| Author(s): | Walczak MJ; Samatanga B; van Drogen F; Peter M; Jelesarov I; Wider G; |
| Address: | "Institute of Molecular Biology and Biophysics, ETH Zurich, Otto-Stern-Weg 5, 8093 Zurich (Switzerland)" |
| ISSN/ISBN: | 1521-3773 (Electronic) 1433-7851 (Linking) |
| Abstract: | "Ste5 is a scaffold protein that controls the pheromone response of the MAP-kinase cascade in yeast cells. Upon pheromone stimulation, Ste5 (through its RING-H2 domain) interacts with the beta and gamma subunits of an activated heterodimeric G protein and promotes activation of the MAP-kinase cascade. With structural and biophysical studies, we show that the Ste5 RING-H2 domain exists as a molten globule under native buffer conditions, in yeast extracts, and even in denaturing conditions containing urea (7 M). Furthermore, it exhibits high thermal stability in native conditions. Binding of the Ste5 RING-H2 domain to the physiological Gbeta/gamma (Ste4/Ste18) ligand is accompanied by a conformational transition into a better folded, more globular structure. This study reveals novel insights into the folding mechanism and recruitment of binding partners by the Ste5 RING-H2 domain. We speculate that many RING domains may share a similar mechanism of substrate recognition and molten-globule-like character" |
| Keywords: | "Adaptor Proteins, Signal Transducing/*chemistry/metabolism GTP-Binding Protein beta Subunits/chemistry/metabolism GTP-Binding Protein gamma Subunits/chemistry/metabolism Mercaptoethanol/chemistry Nuclear Magnetic Resonance, Biomolecular Protein Folding Pr;" |
| Notes: | "MedlineWalczak, Michal J Samatanga, Brighton van Drogen, Frank Peter, Matthias Jelesarov, Ilian Wider, Gerhard eng Research Support, Non-U.S. Gov't Germany 2013/12/21 Angew Chem Int Ed Engl. 2014 Jan 27; 53(5):1320-3. doi: 10.1002/anie.201306702. Epub 2013 Dec 16" |
