NMR NMR analysis of the backbone dynamics of the small GTP GTP ase Rheb and its interaction with the regulatory protein FKBP FKBP 38

摘要

Ras homolog enriched in brain (Rheb) is a small GTP ase that regulates mammalian/mechanistic target of rapamycin complex 1 ( mTORC 1) and, thereby, cell growth and metabolism. Here we show that cycling between the inactive GDP ‐ and the active GTP ‐bound state modulates the backbone dynamics of a C‐terminal truncated form, RhebΔ CT , which is suggested to influence its interactions. We further investigated the interactions between RhebΔ CT and the proposed Rheb‐binding domain of the regulatory protein FKBP 38. The observed weak interactions with the GTP ‐analogue‐ (Gpp NH p‐) but not the GDP ‐bound state, appear to accelerate the GDP to GTP exchange, but only very weakly compared to a genuine GEF . Thus, FKBP 38 is most likely not a GEF but a Rheb effector that may function in membrane targeting of Rheb.