The RING domain of the scaffold protein Ste5 adopts a molten globular character with high thermal and chemical stability

Angewandte Chemie
Michal J WalczakGerhard Wider

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 β and γ 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 Gβ/γ (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.

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Citations

Jan 30, 2016·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Zhenhua HuElaine A Elion
May 23, 2015·Bioinformatics·Piotr KlukowskiGerhard Wider
Feb 20, 2016·Acta Crystallographica. Section D, Structural Biology·Laura E BakerZygmunt S Derewenda
Jul 19, 2019·The Journal of Cell Biology·Frank van DrogenMatthias Peter

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