Abstract
In response to environmental stress, cells often generate pH signals that serve to protect vital cellular components and reprogram gene expression for survival. A major barrier to our understanding of this process has been the identification of signaling proteins that detect changes in intracellular pH. To identify candidate pH sensors, we developed a computer algorithm that searches proteins for networks of proton-binding sidechains. This analysis indicates that Gα subunits, the principal transducers of G protein-coupled receptor (GPCR) signals, are pH sensors. Our structure-based calculations and biophysical investigations reveal that Gα subunits contain networks of pH-sensing sidechains buried between their Ras and helical domains. Further, we show that proton binding induces changes in conformation that promote Gα phosphorylation and suppress receptor-initiated signaling. Together, our computational, biophysical, and cellular analyses reveal an unexpected function for G proteins as mediators of stress-response signaling.
Original language | English (US) |
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Pages (from-to) | 531-538 |
Number of pages | 8 |
Journal | Molecular Cell |
Volume | 51 |
Issue number | 4 |
DOIs | |
State | Published - Aug 22 2013 |
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology