Farnesylation of Pex19p is required for its structural integrity and function in Peroxisome Biogenesis

Rucktaschel, Robert, Thoms, Sven, Sidorovitch, Vadim, Halbach, Andre, Pechlivanis, Markos, Volkmer, Rudolf, Alexandrov, Kirill, Kuhlmann, Jürgen, Rottensteiner, Hanspeter and Erdmann, Ralf (2009) Farnesylation of Pex19p is required for its structural integrity and function in Peroxisome Biogenesis. Journal of Biological Chemistry, 284 31: 20885-20896. doi:10.1074/jbc.M109.016584

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Author Rucktaschel, Robert
Thoms, Sven
Sidorovitch, Vadim
Halbach, Andre
Pechlivanis, Markos
Volkmer, Rudolf
Alexandrov, Kirill
Kuhlmann, Jürgen
Rottensteiner, Hanspeter
Erdmann, Ralf
Title Farnesylation of Pex19p is required for its structural integrity and function in Peroxisome Biogenesis
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2009-07-31
Year available 2009
Sub-type Article (original research)
DOI 10.1074/jbc.M109.016584
Open Access Status File (Publisher version)
Volume 284
Issue 31
Start page 20885
End page 20896
Total pages 12
Editor Herbert Tabor
Place of publication Bethesda, MD
Publisher American Society for Biochemistry and Molecular Biology
Collection year 2010
Language eng
Subject 06 Biological Sciences
0601 Biochemistry and Cell Biology
970106 Expanding Knowledge in the Biological Sciences
060107 Enzymes
Abstract The conserved CaaX box peroxin Pex19p is known to be modified by farnesylation. The possible involvement of this lipid modification in peroxisome biogenesis, the degree to which Pex19p is farnesylated, and its molecular function are unknown or controversial. We resolve these issues by first showing that the complete pool of Pex19p is processed by farnesyltransferase in vivo and that this modification is independent of peroxisome induction or the Pex19p membrane anchor Pex3p. Furthermore, genomic mutations of PEX19 prove that farnesylation is essential for proper matrix protein import into peroxisomes, which is supposed to be caused indirectly by a defect in peroxisomal membrane protein (PMP) targeting or stability. This assumption is corroborated by the observation that mutants defective in Pex19p farnesylation are characterized by a significantly reduced steady-state concentration of prominent PMPs (Pex11p, Ant1p) but also of essential components of the peroxisomal import machinery, especially the RING peroxins, which were almost depleted from the importomer. In vivo and in vitro, PMP recognition is only efficient when Pex19p is farnesylated with affinities differing by a factor of 10 between the non-modified and wild-type forms of Pex19p. Farnesylation is likely to induce a conformational change in Pex19p. Thus, isoprenylation of Pex19p contributes to substrate membrane protein recognition for the topogenesis of PMPs, and our results highlight the importance of lipid modifications in protein-protein interactions.
Keyword Circular-dichroism Spectra
Protein secondary structure
Molecular Characterization
Import receptor
Potential role
Q-Index Code C1
Q-Index Status Confirmed Code

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Created: Tue, 17 Nov 2009, 12:10:00 EST