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000303258 1001_ $$00000-0002-7752-9581$$aChen, Walter W$$b0
000303258 245__ $$aPEX39 facilitates the peroxisomal import of PTS2-containing proteins.
000303258 260__ $$aNew York, NY$$bNature America$$c2025
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000303258 520__ $$aPeroxisomes are metabolic organelles essential for human health. Defects in peroxisomal biogenesis proteins (also known as peroxins (PEXs)) cause devastating disease. PEX7 binds proteins containing a type 2 peroxisomal targeting signal (PTS2) to enable their import from the cytosol into peroxisomes, although many aspects of this process remain enigmatic. Utilizing in vitro assays, yeast and human cells, we show that PEX39, a previously uncharacterized protein, is a cytosolic peroxin that facilitates the import of PTS2-containing proteins by binding PEX7 and stabilizing its interaction with cargo proteins containing a PTS2. PEX39 and PEX13, a peroxisomal membrane translocon protein, both possess an (R/K)PWE motif necessary for PEX7 binding. Handover of PEX7 from PEX39 to PEX13 via these motifs provides a new paradigm for peroxisomal protein import and biogenesis. Collectively, this work reveals how PEX39 and (R/K)PWE motifs facilitate the import of PTS2-containing proteins and advances our understanding of peroxisomal disease.
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000303258 7001_ $$00000-0003-2311-8258$$aRodrigues, Tony A$$b1
000303258 7001_ $$00000-0001-7445-4978$$aWendscheck, Daniel$$b2
000303258 7001_ $$00000-0001-8887-2046$$aPedrosa, Ana G$$b3
000303258 7001_ $$aYang, Chendong$$b4
000303258 7001_ $$00000-0003-3571-5164$$aFrancisco, Tânia$$b5
000303258 7001_ $$0P:(DE-He78)4e7fd3fe1ca5ba94d2248f767310029d$$aMöcklinghoff, Till$$b6$$udkfz
000303258 7001_ $$aZografakis, Alexandros$$b7
000303258 7001_ $$aNunes-Silva, Bernardo$$b8
000303258 7001_ $$aAvraham, Reut E$$b9
000303258 7001_ $$aSilva, Ana R$$b10
000303258 7001_ $$aFerreira, Maria J$$b11
000303258 7001_ $$00009-0009-6060-1557$$aDas, Hirak$$b12
000303258 7001_ $$aKoster, Janet$$b13
000303258 7001_ $$aNeuwirth, Simone$$b14
000303258 7001_ $$00000-0003-3316-9999$$aBender, Julian$$b15
000303258 7001_ $$00000-0001-8908-4295$$aOeljeklaus, Silke$$b16
000303258 7001_ $$00000-0002-0253-7624$$aSondhi, Varun$$b17
000303258 7001_ $$00000-0002-4922-4545$$aGatsogiannis, Christos$$b18
000303258 7001_ $$00000-0001-9947-115X$$aSchuldiner, Maya$$b19
000303258 7001_ $$aZalckvar, Einat$$b20
000303258 7001_ $$00000-0002-2289-9083$$aHofmann, Kay$$b21
000303258 7001_ $$aWaterham, Hans R$$b22
000303258 7001_ $$00000-0002-2705-7432$$aDeBerardinis, Ralph J$$b23
000303258 7001_ $$00000-0001-7714-5302$$aAzevedo, Jorge E$$b24
000303258 7001_ $$00000-0001-5096-1975$$aWarscheid, Bettina$$b25
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