Structure-guided mutation of the conserved G3-box glycine in rheb generates a constitutively activated regulator of mammalian target of rapamycin (mTOR)

Abstract

Background: GTPases regulate cellular signaling by cycling between GDP-(inactive) and GTP-(active) bound states. Results: Rheb GTPase cycling was manipulated by structure- guided mutagenesis of an ultraconserved residue. Conclusion: Constitutively activated or inactive Rheb mutants were generated by substitutions that displace the hydrolytic water or β-cells-phosphate, respectively. Significance: These mutants offer new research tools, and the approach may be extended to other GTPases. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.