NMR analysis of the backbone dynamics of the small GTPase Rheb and its interaction with the regulatory protein FKBP38
NMR analysis of the backbone dynamics of the small GTPase Rheb and its interaction with the regulatory protein FKBP38
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DOI：
10.1002/1873-3468.12925
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发表时间：
2018-01
期刊：
影响因子：
3.5
通讯作者：
Maristella De Cicco;L. Kiss;S. Dames
中科院分区：
文献类型：
--
作者：
Maristella De Cicco;L. Kiss;S. Dames
脑中富集的Ras同源物（Rheb）是一种小的GTdR，其调节雷帕霉素复合物1（mTORC 1）的哺乳动物/机械靶标，从而调节细胞生长和代谢。在这里，我们表明，非活性GDP-和活性GTP-结合状态之间的循环调节C-末端截短形式RhebΔCT的骨架动力学，这被认为会影响其相互作用。我们进一步研究了RhebΔCT与调控蛋白FKBP 38的Rheb结合结构域之间的相互作用。观察到的与GTP类似物（GppNHp）而不是GDP结合态的弱相互作用似乎加速了GDP到GTP的交换，但与真正的GEF相比非常微弱。因此，FKBP 38最有可能不是GEF，而是Rheb效应物，其可在Rheb的膜靶向中起作用。
Ras homolog enriched in brain (Rheb) is a small GTPase that regulates mammalian/mechanistic target of rapamycin complex 1 (mTORC1) 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, RhebΔCT, which is suggested to influence its interactions. We further investigated the interactions between RhebΔCT and the proposed Rheb‐binding domain of the regulatory protein FKBP38. The observed weak interactions with the GTP‐analogue‐ (GppNHp‐) but not the GDP‐bound state, appear to accelerate the GDP to GTP exchange, but only very weakly compared to a genuine GEF. Thus, FKBP38 is most likely not a GEF but a Rheb effector that may function in membrane targeting of Rheb.