Analysis of the eukaryotic prenylome by isoprenoid affinity tagging

Nguyen, Uyen T. T., Guo, Zhong, Delon, Christine, Wu, Yaowen, Deraeve, Celine, Fraenzel, Benjamin, Bon, Robin S., Blankenfeldt, Wulf, Goody, Roger S., Waldmann, Herbert, Wolters, Dirk and Alexandrov, Kirill (2009) Analysis of the eukaryotic prenylome by isoprenoid affinity tagging. Nature Chemical Biology, 5 4: 227-235. doi:10.1038/nchembio.149


Author Nguyen, Uyen T. T.
Guo, Zhong
Delon, Christine
Wu, Yaowen
Deraeve, Celine
Fraenzel, Benjamin
Bon, Robin S.
Blankenfeldt, Wulf
Goody, Roger S.
Waldmann, Herbert
Wolters, Dirk
Alexandrov, Kirill
Title Analysis of the eukaryotic prenylome by isoprenoid affinity tagging
Journal name Nature Chemical Biology   Check publisher's open access policy
ISSN 1552-4450
Publication date 2009-04
Sub-type Article (original research)
DOI 10.1038/nchembio.149
Volume 5
Issue 4
Start page 227
End page 235
Total pages 9
Editor Terry L. Shepherd
Philip Campbell
Linda Miller
Place of publication London, U.K.
Publisher Nature Publishing Group
Collection year 2010
Language eng
Subject 03 Chemical Sciences
0601 Biochemistry and Cell Biology
C1
970106 Expanding Knowledge in the Biological Sciences
060107 Enzymes
Abstract Protein prenylation is a widespread phenomenon in eukaryotic cells that affects many important signaling molecules. We describe the structure-guided design of engineered protein prenyltransferases and their universal synthetic substrate, biotin-geranylpyrophosphate. These new tools allowed us to detect femtomolar amounts of prenylatable proteins in cells and organs and to identify their cognate protein prenyltransferases. Using this approach, we analyzed the in vivo effects of protein prenyltransferase inhibitors. Whereas some of the inhibitors displayed the expected activities, others lacked in vivo activity or targeted a broader spectrum of prenyltransferases than previously believed. To quantitate the in vivo effect of the prenylation inhibitors, we profiled biotin-geranyl–tagged RabGTPases across the proteome by mass spectrometry. We also demonstrate that sites of active vesicular transport carry most of the RabGTPases. This approach enables a quantitative proteome-wide analysis of the regulation of protein prenylation and its modulation by therapeutic agents.
Keyword Protein prenylation
Q-Index Code C1
Q-Index Status Confirmed Code

 
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Created: Thu, 03 Sep 2009, 08:28:30 EST by Mr Andrew Martlew on behalf of Institute for Molecular Bioscience