The <i>Hansenula polymorpha</i> peroxisomal targeting signal 1 receptor, Pex5p, functions as a tetramer

Moscicka, Katarzyna B.; Klompmaker, Sandra H.; Wang, Dongyuan; Klei, Ida J. van der; Boekema, Egbert J.

doi:10.1016/j.febslet.2007.03.061

Cited by 17 publications

(20 citation statements)

References 18 publications

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“…These same data also provided the molecular basis to explain why Pex5p, a monomeric protein in solution [41], displays such a high Stokes radius. Despite these observations we note that some researchers still assume that Pex5p is a globular protein and have even proposed that this peroxin is a homotetrameric protein [42]. The only piece of evidence that has been used to support this idea comes from electron microscopy analysis of negatively stained recombinant Pex5p, which revealed square-shaped particles with a diameter of 11.5 -13.4 nm [42].…”

Section: Peroxisomal Matrix Proteins and Their Receptorsmentioning

confidence: 85%

“…Despite these observations we note that some researchers still assume that Pex5p is a globular protein and have even proposed that this peroxin is a homotetrameric protein [42]. The only piece of evidence that has been used to support this idea comes from electron microscopy analysis of negatively stained recombinant Pex5p, which revealed square-shaped particles with a diameter of 11.5 -13.4 nm [42]. Unfortunately, besides the fact that one of the dimensions of these particles had to be guessed so that their volume/mass could be estimated, no data were provided confirming that the observed particles are indeed Pex5p molecules and not Escherichia coli contaminants.…”

Section: Peroxisomal Matrix Proteins and Their Receptorsmentioning

confidence: 85%

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The peroxisomal protein import machinery – a case report of transient ubiquitination with a new flavor

Grou

Carvalho

Pinto

et al. 2008

Cell. Mol. Life Sci.

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The peroxisomal protein import machinery displays remarkable properties. Be it its capacity to accept already folded proteins as substrates, its complex architecture or its energetics, almost every aspect of this machinery seems unique. The list of unusual properties is still growing as shown by the recent finding that one of its central components, Pex5p, is transiently monoubiquitinated at a cysteine residue. However, the data gathered in recent years also suggest that the peroxisomal import machinery is not that exclusive and similarities with p97/Cdc48-mediated processes and with multisubunit RING-E3 ligases are starting to emerge. Here, we discuss these data trying to distill the principles by which this complex machinery operates.

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Section: Peroxisomal Matrix Proteins and Their Receptorsmentioning

confidence: 85%

Section: Peroxisomal Matrix Proteins and Their Receptorsmentioning

confidence: 85%

The peroxisomal protein import machinery – a case report of transient ubiquitination with a new flavor

Grou

Carvalho

Pinto

et al. 2008

Cell. Mol. Life Sci.

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“…In higher eukaryotes (plants, mammals), Pex5p and Pex7p interact with Pex13p and Pex14p at the peroxisomal membrane during the docking step of peroxisomal protein import, whereas in lower eukaryotes (yeast, fungi), they bind to Pex13p, Pex14p, and Pex17p (41). EM studies have revealed that Hansenula polymorpha Pex5p(F) (Hp Pex5p) is a globular tetramer near pH 7 which exists in two forms (open/closed) and undergoes a conformational change upon interaction with Hp Pex20p (42). A large conformational change was also observed by fluorescence spectroscopy in Hp Pex5p upon interaction with Hp Pex8p, an intraperoxisomal protein for which there is no equivalent in humans (18).…”

Section: Discussionmentioning

confidence: 99%

Solution Structure of Human Pex5·Pex14·PTS1 Protein Complexes Obtained by Small Angle X-ray Scattering

Shiozawa

Konarev

Neufeld

et al. 2009

Journal of Biological Chemistry

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The Pex5p receptor recognizes newly synthesized peroxisomal matrix proteins which have a C-terminal peroxisomal targeting signal to the peroxisome. After docking to protein complexes on the membrane, these proteins are translocated across the membrane. The docking mechanism remains unclear, as no structural data on the multicomponent docking complex are available. As the interaction of the cargo-loaded Pex5p receptor and the peroxisomal membrane protein Pex14p is the essential primary docking step, we have investigated the solution structure of these complexes by small angle x-ray scattering and static light scattering. Titration studies yielded a 1:6 stoichiometry for the Pex5p⅐Pex14p complex, and low resolution structural models were reconstructed from the x-ray scattering data. The free full-length human Pex5p is monomeric in solution, with an elongated, partially unfolded N-terminal domain. The model of the complex reveals that the N terminus of Pex5p remains extended in the presence of cargo and Pex14p, the latter proteins being significantly intermingled with the Pex5p moiety. These results suggest that the extended structure of Pex5p may play a role in interactions with other substrates such as lipids and membrane proteins during the formation of functional multiprotein complexes.

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“…Conversely, Harper et al (2003) saw no effect of HSP70 on the binding of a PTS1 peptide to Pex5p. However, there have been several reports which support the conformational change of Pex5p when bound to a cargo molecule (Madrid et al, 2004;Costa-Rodrigues et al, 2005;Stanley et al, 2006;Moscicka et al, 2007). An N526K mutation at the C-terminus of HsPEX5L (equivalent to N489K in PEX5S; Table 1 and Figure 2B) has been shown to block the binding of PTS1 and induce a conformational shift in the N-terminus.…”

Section: Pex5p Receptormentioning

confidence: 99%

“…There is still a paucity of data concerning the order, affinity and stoichiometries of many of these interactions. Controversy exists as to whether PEX5 binds cargo as a monomer (Costa-Rodrigues et al, 2005), dimer or tetramer (Madrid et al, 2004;Moscicka et al, 2007). However, more recent studies are consistent with a monomeric solution structure (Shiozawa et al, 2009).…”

Section: Stoichiometry Affinity and Order Of Binding Interactions Ammentioning

confidence: 99%

Getting a camel through the eye of a needle: the import of folded proteins by peroxisomes

Lanyon‐Hogg

Warriner

Baker

2010

Biology of the Cell

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Peroxisomes are a family of organelles which have many unusual features. They can arise de novo from the endoplasmic reticulum by a still poorly characterized process, yet possess a unique machinery for the import of their matrix proteins. As peroxisomes lack DNA, their function, which is highly variable and dependent on developmental and/or environmental conditions, is determined by the post-translational import of specific metabolic enzymes in folded or oligomeric states. The two classes of matrix targeting signals for peroxisomal proteins [PTS1 (peroxisomal targeting signal 1) and PTS2] are recognized by cytosolic receptors [PEX5 (peroxin 5) and PEX7 respectively] which escort their cargo proteins to, or possibly across, the peroxisome membrane. Although the membrane translocation mechanism remains unclear, it appears to be driven by thermodynamically favourable binding interactions. Recycling of the receptors from the peroxisome membrane requires ATP hydrolysis for two linked processes: ubiquitination of PEX5 (and the PEX7 co-receptors in yeast) and the function of two peroxisome-associated AAA (ATPase associated with various cellular activities) ATPases, which play a role in recycling or turnover of the ubiquitinated receptors. This review summarizes and integrates recent findings on peroxisome matrix protein import from yeast, plant and mammalian model systems, and discusses some of the gaps in our understanding of this remarkable protein transport system.

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The Hansenula polymorpha peroxisomal targeting signal 1 receptor, Pex5p, functions as a tetramer

Abstract: We have studied Hansenula polymorpha Pex5p and Pex20p, peroxins involved in peroxisomal matrix protein import.

Cited by 17 publications

References 18 publications

The peroxisomal protein import machinery – a case report of transient ubiquitination with a new flavor

The peroxisomal protein import machinery – a case report of transient ubiquitination with a new flavor

Solution Structure of Human Pex5·Pex14·PTS1 Protein Complexes Obtained by Small Angle X-ray Scattering

Getting a camel through the eye of a needle: the import of folded proteins by peroxisomes

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