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Allosteric modulation of peroxisomal membrane protein recognition by farnesylation of the peroxisomal import receptor PEX19.

Emmanouilidis L, Schütz U, Tripsianes K, Madl T, Radke J, Rucktäschel R, Wilmanns M, Schliebs W, Erdmann R, Sattler M
Nat Commun 8 14635 (2017)
Cited: 24 times
EuropePMC logo PMID: 28281558

Abstract

The transport of peroxisomal membrane proteins (PMPs) requires the soluble PEX19 protein as chaperone and import receptor. Recognition of cargo PMPs by the C-terminal domain (CTD) of PEX19 is required for peroxisome biogenesis in vivo. Farnesylation at a C-terminal CaaX motif in PEX19 enhances the PMP interaction, but the underlying molecular mechanisms are unknown. Here, we report the NMR-derived structure of the farnesylated human PEX19 CTD, which reveals that the farnesyl moiety is buried in an internal hydrophobic cavity. This induces substantial conformational changes that allosterically reshape the PEX19 surface to form two hydrophobic pockets for the recognition of conserved aromatic/aliphatic side chains in PMPs. Mutations of PEX19 residues that either mediate farnesyl contacts or are directly involved in PMP recognition abolish cargo binding and cannot complement a ΔPEX19 phenotype in human Zellweger patient fibroblasts. Our results demonstrate an allosteric mechanism for the modulation of protein function by farnesylation.

Articles - 5lnf mentioned but not cited (3)

  1. Allosteric modulation of peroxisomal membrane protein recognition by farnesylation of the peroxisomal import receptor PEX19. Emmanouilidis L, Schütz U, Tripsianes K, Madl T, Radke J, Rucktäschel R, Wilmanns M, Schliebs W, Erdmann R, Sattler M. Nat Commun 8 14635 (2017)
  2. Effect of Cathode Microstructure on Electrochemical Properties of Sodium Nickel-Iron Chloride Batteries. Ahn BM, Ahn CW, Hahn BD, Choi JJ, Kim YD, Lim SK, Choi JH. Materials (Basel) 14 5605 (2021)
  3. Selective isotope labeling for NMR structure determination of proteins in complex with unlabeled ligands. Tripsianes K, Schütz U, Emmanouilidis L, Gemmecker G, Sattler M. J. Biomol. NMR 73 183-189 (2019)


Reviews citing this publication (5)

  1. Paramagnetic Chemical Probes for Studying Biological Macromolecules. Miao Q, Nitsche C, Orton H, Overhand M, Otting G, Ubbink M. Chem Rev 122 9571-9642 (2022)
  2. Peroxisome biogenesis, membrane contact sites, and quality control. Farré JC, Mahalingam SS, Proietto M, Subramani S. EMBO Rep. 20 (2019)
  3. The peroxisome biogenesis factors Pex3 and Pex19: multitasking proteins with disputed functions. Jansen RLM, van der Klei IJ. FEBS Lett 593 457-474 (2019)
  4. Peroxisome prognostications: Exploring the birth, life, and death of an organelle. Mast FD, Rachubinski RA, Aitchison JD. J Cell Biol 219 (2020)
  5. Biogenesis and Function of Peroxisomes in Human Disease with a Focus on the ABC Transporter. Imanaka T. Biol Pharm Bull 42 649-665 (2019)

Articles citing this publication (16)

  1. Comparative Genomics of Peroxisome Biogenesis Proteins: Making Sense of the PEX Proteins. Jansen RLM, Santana-Molina C, van den Noort M, Devos DP, van der Klei IJ. Front Cell Dev Biol 9 654163 (2021)
  2. Conformational Sampling of the Intrinsically Disordered C-Terminal Tail of DERA Is Important for Enzyme Catalysis. Schulte M, Petrović D, Neudecker P, Hartmann R, Pietruszka J, Willbold S, Willbold D, Panwalkar V. ACS Catal 8 3971-3984 (2018)
  3. A bench stable formal Cu(iii) N-heterocyclic carbene accessible from simple copper(ii) acetate. Ghavami ZS, Anneser MR, Kaiser F, Altmann PJ, Hofmann BJ, Schlagintweit JF, Grivani G, Kühn FE. Chem Sci 9 8307-8314 (2018)
  4. Atomic resolution protein allostery from the multi-state structure of a PDZ domain. Ashkinadze D, Kadavath H, Pokharna A, Chi CN, Friedmann M, Strotz D, Kumari P, Minges M, Cadalbert R, Königl S, Güntert P, Vögeli B, Riek R. Nat Commun 13 6232 (2022)
  5. Delineating transitions during the evolution of specialised peroxisomes: Glycosome formation in kinetoplastid and diplonemid protists. Andrade-Alviárez D, Bonive-Boscan AD, Cáceres AJ, Quiñones W, Gualdrón-López M, Ginger ML, Michels PAM. Front Cell Dev Biol 10 979269 (2022)
  6. Dengue and Zika Virus Capsid Proteins Contain a Common PEX19-Binding Motif. Farelo MA, Korrou-Karava D, Brooks KF, Russell TA, Maringer K, Mayerhofer PU. Viruses 14 253 (2022)
  7. Fatty Liver Due to Increased de novo Lipogenesis: Alterations in the Hepatic Peroxisomal Proteome. Knebel B, Fahlbusch P, Dille M, Wahlers N, Hartwig S, Jacob S, Kettel U, Schiller M, Herebian D, Koellmer C, Lehr S, Müller-Wieland D, Kotzka J. Front Cell Dev Biol 7 248 (2019)
  8. Functional Analyses of a Putative, Membrane-Bound, Peroxisomal Protein Import Mechanism from the Apicomplexan Protozoan Toxoplasma gondii. Mbekeani AJ, Stanley WA, Kalel VC, Dahan N, Zalckvar E, Sheiner L, Schliebs W, Erdmann R, Pohl E, Denny PW. Genes (Basel) 9 (2018)
  9. Integrative Informatics Analysis of Transcriptome and Identification of Interacted Genes in the Glomeruli and Tubules in CKD. Liu L, Ma F, Hao Y, Yi Z, Yu X, Xu B, Wei C, Hu J. Front Med (Lausanne) 7 615306 (2020)
  10. NMR characterization of solvent accessibility and transient structure in intrinsically disordered proteins. Hartlmüller C, Spreitzer E, Göbl C, Falsone F, Madl T. J. Biomol. NMR 73 305-317 (2019)
  11. PEX19 Coordinates Neutral Lipid Storage in Cells in a Peroxisome-Independent Fashion. Lyschik S, Lauer AA, Roth T, Janitschke D, Hollander M, Will T, Hartmann T, Kopito RR, Helms V, Grimm MOW, Schrul B. Front Cell Dev Biol 10 859052 (2022)
  12. Prenylated PALM2 Promotes the Migration of Esophageal Squamous Cell Carcinoma Cells Through Activating Ezrin. Deng DX, Li CY, Zheng ZY, Wen B, Liao LD, Zhang XJ, Li EM, Xu LY. Mol Cell Proteomics 22 100593 (2023)
  13. Protein Isoprenylation in Yeast Targets COOH-Terminal Sequences Not Adhering to the CaaX Consensus. Berger BM, Kim JH, Hildebrandt ER, Davis IC, Morgan MC, Hougland JL, Schmidt WK. Genetics 210 1301-1316 (2018)
  14. Recognition and Chaperoning by Pex19, Followed by Trafficking and Membrane Insertion of the Peroxisome Proliferation Protein, Pex11. Zientara-Rytter KM, Mahalingam SS, Farré JC, Carolino K, Subramani S. Cells 11 157 (2022)
  15. Specific Disruption of Ras2 CAAX Proteolysis Alters Its Localization and Function. Ravishankar R, Hildebrandt ER, Greenway G, Asad N, Gore S, Dore TM, Schmidt WK. Microbiol Spectr 11 e0269222 (2023)
  16. The peroxisome biogenesis factors posttranslationally target reticulon homology domain-containing proteins to the endoplasmic reticulum membrane. Yamamoto Y, Sakisaka T. Sci Rep 8 2322 (2018)


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