Recognition and Chaperoning by Pex19, Followed by Trafficking and Membrane Insertion of the Peroxisome Proliferation Protein, Pex11.
| Title: | Recognition and Chaperoning by Pex19, Followed by Trafficking and Membrane Insertion of the Peroxisome Proliferation Protein, Pex11. |
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| Authors: | Zientara-Rytter KM; Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, CA 92093-0322, USA.; Mahalingam SS; Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, CA 92093-0322, USA.; Farré JC; Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, CA 92093-0322, USA.; Carolino K; Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, CA 92093-0322, USA.; Subramani S; Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, CA 92093-0322, USA. |
| Source: | Cells [Cells] 2022 Jan 04; Vol. 11 (1). Date of Electronic Publication: 2022 Jan 04. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural |
| Language: | English |
| Journal Info: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI |
| MeSH Terms: | Membrane Proteins/*metabolism ; Molecular Chaperones/*metabolism; Amino Acid Sequence ; Cell Proliferation ; Humans |
| Abstract: | Pex11, an abundant peroxisomal membrane protein (PMP), is required for division of peroxisomes and is robustly imported to peroxisomal membranes. We present a comprehensive analysis of how the Pichia pastoris Pex11 is recognized and chaperoned by Pex19, targeted to peroxisome membranes and inserted therein. We demonstrate that Pex11 contains one Pex19-binding site (Pex19-BS) that is required for Pex11 insertion into peroxisomal membranes by Pex19, but is non-essential for peroxisomal trafficking. We provide extensive mutational analyses regarding the recognition of Pex19-BS in Pex11 by Pex19. Pex11 also has a second, Pex19-independent membrane peroxisome-targeting signal (mPTS) that is preserved among Pex11-family proteins and anchors the human HsPex11γ to the outer leaflet of the peroxisomal membrane. Thus, unlike most PMPs, Pex11 can use two mechanisms of transport to peroxisomes, where only one of them depends on its direct interaction with Pex19, but the other does not. However, Pex19 is necessary for membrane insertion of Pex11. We show that Pex11 can self-interact, using both homo- and/or heterotypic interactions involving its N-terminal helical domains. We demonstrate that Pex19 acts as a chaperone by interacting with the Pex19-BS in Pex11, thereby protecting Pex11 from spontaneous oligomerization that would otherwise cause its aggregation and subsequent degradation. |
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| Grant Information: | R01 DK041737 United States DK NIDDK NIH HHS |
| Contributed Indexing: | Keywords: Pex11; Pex19; peroxisomal membrane protein; peroxisome division; peroxisome proliferation protein |
| Substance Nomenclature: | 0 (Membrane Proteins); 0 (Molecular Chaperones); 0 (PEX11A protein, human); 157153-79-2 (PEX19 protein, human) |
| Entry Date(s): | Date Created: 20220111 Date Completed: 20220330 Latest Revision: 20230223 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC8750153 |
| DOI: | 10.3390/cells11010157 |
| PMID: | 35011719 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural