Cytosolic factors mediate protein insertion into the peroxisomal membrane

Pause, Birgit; Diestelkötter, Petra; Heid, Hans; Just, Wilhelm W.

doi:10.1016/s0014-5793(97)00975-7

Cited by 39 publications

(34 citation statements)

References 22 publications

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“…Our results are consistent with the earlier observations as follows. PMP22 forms two types of complexes in the postribosomal supernatant (29). One of them includes TCP1 ring complex, which is the eukaryotic GroEL equivalent, and the other includes a 40-kDa protein, which is expected to be Pex19p.…”

Section: Discussionmentioning

confidence: 99%

Domain Architecture and Activity of Human Pex19p, a Chaperone-like Protein for Intracellular Trafficking of Peroxisomal Membrane Proteins

Shibata

Kashiwayama

Imanaka

et al. 2004

Journal of Biological Chemistry

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Pex19p is a peroxin involved in peroxisomal membrane biogenesis and probably functions as a chaperone and/or soluble receptor specific for cargo peroxisomal membrane proteins (PMPs). To elucidate the functional constituents of Pex19p in terms of the protein structure, we investigated its domain architecture and binding affinity toward various PMPs and peroxins. The human Pex19p cDNA was overexpressed in Escherichia coli, and a highly purified sample of the Pex19p protein was prepared. When PMP22 was synthesized by cell-free translation in the presence of Pex19p, the PMP22 bound to Pex19p was soluble, whereas PMP22 alone was insoluble. This observation shows that Pex19p plays a role in capturing PMP and maintaining its solubility. In a similar manner, Pex19p was bound to PMP70 and Pex16p as well as the Pex3p soluble fragment. Limited proteolysis analyses revealed that Pex19p consists of the C-terminal core domain flanking the flexible N-terminal region. Separation of Pex19p into its N-and C-terminal halves abolished interactions with PMP22, PMP70, and Pex16p. In contrast, the flexible N-terminal half of Pex19p was bound to the Pex3p soluble fragment, suggesting that the binding mode of Pex3p toward Pex19p differs from that of other PMPs. This idea is supported by our detection of the Pex19p-Pex3p-PMP22 ternary complex.

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Section: Discussionmentioning

confidence: 99%

Domain Architecture and Activity of Human Pex19p, a Chaperone-like Protein for Intracellular Trafficking of Peroxisomal Membrane Proteins

Shibata

Kashiwayama

Imanaka

et al. 2004

Journal of Biological Chemistry

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“…Although there are several studies that support the existence of an mPTS1-mediated pathway (7)(8)(9)(10)(11)(12)(13)(14), evidence for a twomPTS model comes primarily from studies of another tailanchored PMP, namely S. cerevisiae Pex15p. Elgersma et al (15) demonstrate that the C-terminal 82-amino acid residues including the positively charged domain (KKYK) and immediately adjacent single TMD of Pex15p were sufficient for sorting a reporter protein to both peroxisomes and ER.…”

Section: Discussionmentioning

confidence: 99%

“…Data on the routing of PMPs directly to the peroxisomal boundary membrane has been derived mostly from in vitro studies (7)(8)(9)(10). Direct sorting of PMPs appears to be mediated by molecular chaperones and a two-step binding and insertion process that is temperature-dependent but does not require ATP hydrolysis.…”

mentioning

confidence: 99%

The Sorting Signals for Peroxisomal Membrane-bound Ascorbate Peroxidase Are within Its C-terminal Tail

Mullen

Trelease

2000

Journal of Biological Chemistry

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Peroxisomal ascorbate peroxidase (APX) is a carboxyl tail-anchored, type II (N cytosol -C matrix ) integral membrane protein that functions in the regeneration of NAD ؉ in glyoxysomes of germinated oilseeds and protection of peroxisomes in other organisms from toxic H 2 O 2 . Recently we showed that cottonseed peroxisomal APX was sorted post-translationally from the cytosol to peroxisomes via a novel reticular/circular membranous network that was interpreted to be a subdomain of the endoplasmic reticulum (ER), named peroxisomal ER (pER). Here we report on the molecular signals responsible for sorting peroxisomal APX. Deletions or site-specific substitutions of certain amino acid residues within the hydrophilic C-terminal-most eight-amino acid residues (includes a positively charged domain found in most peroxisomal integral membrane-destined proteins) abolished sorting of peroxisomal APX to peroxisomes via pER. However, the C-terminal tail was not sufficient for sorting chloramphenicol acetyltransferase to peroxisomes via pER, whereas the peptide plus most of the immediately adjacent 21-amino acid transmembrane domain (TMD) of peroxisomal APX was sufficient for sorting. Replacement of the peroxisomal APX TMD with an artificial TMD (devoid of putative sorting sequences) plus the peroxisomal APX C-terminal tail also sorted chloramphenicol acetyltransferase to peroxisomes via pER, indicating that the peroxisomal APX TMD does not possess essential sorting information. Instead, the TMD appears to confer the proper context required for the conserved positively charged domain to function within peroxisomal APX as an overlapping pER sorting signal and a membrane peroxisome targeting signal type 2.Peroxisomes are single membrane-bound organelles that do not contain DNA nor protein-synthesizing machinery. Data published thus far indicate that they acquire their nuclearencoded matrix and boundary membrane protein constituents from the cytosol in a regulated, post-translational manner. For instance, proteins destined for the peroxisomal matrix are sorted by at least two evolutionarily conserved targeting signals, the type 1 and type 2 peroxisomal targeting signal (PTS).

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“…Experiments conducted with PMP22 in an in vitro transcription and translation system revealed that, in the postribosomal supernatant, PMP22 is present in two polypeptide complexes (26). In complex I, PMP22 is associated with the cytosolic chaperonin TCP1 ring complex (TRiC).…”

mentioning

confidence: 99%

Human Pex19p Binds Peroxisomal Integral Membrane Proteins at Regions Distinct from Their Sorting Sequences

Fransen

Wylin

Brees

et al. 2001

Molecular and Cellular Biology

125

177

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The molecular machinery underlying peroxisomal membrane biogenesis is not well understood. The observation that cells deficient in the peroxins Pex3p, Pex16p, and Pex19p lack peroxisomal membrane structures suggests that these molecules are involved in the initial stages of peroxisomal membrane formation. Pex19p, a predominantly cytosolic protein that can be farnesylated, binds multiple peroxisomal integral membrane proteins, and it has been suggested that it functions as a soluble receptor for the targeting of peroxisomal membrane proteins (PMPs) to the peroxisome. An alternative view proposes that Pex19p functions as a chaperone at the peroxisomal membrane. Here, we show that the peroxisomal sorting determinants and the Pex19p-binding domains of a number of PMPs are distinct entities. In addition, we extend the list of peroxins with which human Pex19p interacts to include the PMP Pex16p and show that Pex19p's CaaX prenylation motif is an important determinant in the affinity of Pex19p for Pex10p, Pex11p␤, Pex12p, and Pex13p.

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Cytosolic factors mediate protein insertion into the peroxisomal membrane

Cited by 39 publications

References 22 publications

Domain Architecture and Activity of Human Pex19p, a Chaperone-like Protein for Intracellular Trafficking of Peroxisomal Membrane Proteins

Domain Architecture and Activity of Human Pex19p, a Chaperone-like Protein for Intracellular Trafficking of Peroxisomal Membrane Proteins

The Sorting Signals for Peroxisomal Membrane-bound Ascorbate Peroxidase Are within Its C-terminal Tail

Human Pex19p Binds Peroxisomal Integral Membrane Proteins at Regions Distinct from Their Sorting Sequences

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