5vxv | pdb_00005vxv
Peroxisomal membrane protein PEX15
Structural highlights
FunctionPEX15_YEAST Essential for the biogenesis of peroxisomes. Has a role in anchoring PEX6 onto the peroxisomal membrane.[1] [2] Publication Abstract from PubMedPex1 and Pex6 form a heterohexameric motor essential for peroxisome biogenesis and function, and mutations in these AAA-ATPases cause most peroxisome-biogenesis disorders in humans. The tail-anchored protein Pex15 recruits Pex1/Pex6 to the peroxisomal membrane, where it performs an unknown function required for matrix-protein import. Here we determine that Pex1/Pex6 from S. cerevisiae is a protein translocase that unfolds Pex15 in a pore-loop-dependent and ATP-hydrolysis-dependent manner. Our structural studies of Pex15 in isolation and in complex with Pex1/Pex6 illustrate that Pex15 binds the N-terminal domains of Pex6, before its C-terminal disordered region engages with the pore loops of the motor, which then processively threads Pex15 through the central pore. Furthermore, Pex15 directly binds the cargo receptor Pex5, linking Pex1/Pex6 to other components of the peroxisomal import machinery. Our results thus support a role of Pex1/Pex6 in mechanical unfolding of peroxins or their extraction from the peroxisomal membrane during matrix-protein import. The peroxisomal AAA-ATPase Pex1/Pex6 unfolds substrates by processive threading.,Gardner BM, Castanzo DT, Chowdhury S, Stjepanovic G, Stefely MS, Hurley JH, Lander GC, Martin A Nat Commun. 2018 Jan 10;9(1):135. doi: 10.1038/s41467-017-02474-4. PMID:29321502[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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