Protons as Second Messenger Regulators of G Protein Signaling》.pdf

Molecular Cell Short Article Protons as Second Messenger Regulators of G Protein Signaling Daniel G. Isom,1,* Vishwajith Sridharan,1 Rachael Baker,1 Sarah T. Clement,1 David M. Smalley,2,3 and Henrik G. Dohlman1,2,* 1Department of Biochemistry and Biophysics 2Department of Pharmacology 3Michael Hooker Proteomics Center University of North Carolina, Chapel Hill, NC 27599, USA *Correspondence: disom@ (D.G.I.), henrik_dohlman@ (H.G.D.) /10.1016/j.molcel.2013.07.012 SUMMARY pH sensors are specialized proteins that couple their biolog- ical function to physiological changes in cellular pH (6 In response to environmental stress, cells often pH 8) (Srivastava et al., 2007). Perhaps the best-known proton generate pH signals that serve to protect vital cellular sensor is hemoglobin, which exhibits reduced affinity for oxygen components and reprogram gene expression for as a consequence of respiratory acidosis in the peripheral survival. A major barrier to our understanding of vasculature (the so-called Bohr effect) (Perutz, 1978). Hemoglo- this process has been the identification of signaling bin and other pH sensors detect changes in cellular pH using sidechains (Asp, Glu, His, Lys, Arg) or sidechain modifications proteins that detect changes in intracellular pH. To (phosphorylation) that bind protons. In these sensors, proton- identify candidate pH sensors, we developed a com- binding groups are organized in structural arrangements that puter algorithm