TY  - JOUR
AU  - Ismail, Shehab A
AU  - Chen, Yong-Xiang
AU  - Rusinova, Alexandra
AU  - Chandra, Anchal
AU  - Bierbaum, Martin
AU  - Gremer, Lothar
AU  - Triola, Gemma
AU  - Waldmann, Herbert
AU  - Bastiaens, Philippe I H
AU  - Wittinghofer, Alfred
TI  - Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for farnesylated cargo
JO  - Nature chemical biology
VL  - 7
IS  - 12
SN  - 1552-4469
CY  - Basingstoke
PB  - Nature Publishing Group
M1  - FZJ-2014-05673
SP  - 942 - 949
PY  - 2011
AB  - Lipidated Rho and Rab GTP-binding proteins are transported between membranes in complex with solubilizing factors called ‘guanine nucleotide dissociation inhibitors’ (GDIs). Unloading from GDIs using GDI displacement factors (GDFs) has been proposed but remains mechanistically elusive. PDEd is a putative solubilizing factor for several prenylated Ras-subfamily proteins. Here we report the structure of fully modified farnesylated Rheb-GDP in complex with PDEd. The structure explains the nucleotide-independent binding of Rheb to PDEd and the relaxed specificity of PDEd. We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. We thus describe a new transport system for farnesylated G proteins involving a GDI-like molecule and an unequivocal GDF. Considering the importance of PDEd for proper Ras and Rheb signaling, this study is instrumental in developing a new target for anticancer therapy.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000297166200018
C6  - pmid:22002721
DO  - DOI:10.1038/nchembio.686
UR  - https://juser.fz-juelich.de/record/172163
ER  -