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de Cicco, M.* ; Kiss, L.* ; Dames, S.A.

NMR analysis of the backbone dynamics of the small GTPase Rheb and its interaction with the regulatory protein FKBP38.

FEBS Lett. 592, 130-146 (2017)
Open Access Green as soon as Postprint is submitted to ZB.
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, RhebDCT, which is suggested to influence its interactions. We further investigated the interactions between RhebDCT 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Backbone Dynamics ; Fkbp38 ; Gtpase ; Nucleotide Exchange Rate ; Protein-protein Interactions ; Rheb; Guanine-nucleotide Exchange; Sequence-specific H-1; Tsc2 Gap Activity; Mammalian Target; Cell-growth; Amino-acids; Conformational States; Inhibits Apoptosis; Rapamycin Mtor; Ras Protein
ISSN (print) / ISBN 0014-5793
e-ISSN 1873-3468
Journal FEBS Letters
Quellenangaben Volume: 592, Issue: 1, Pages: 130-146 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Hoboken
Reviewing status Peer reviewed