8c0v | pdb_00008c0v

Structure of the peroxisomal Pex1/Pex6 ATPase complex bound to a substrate in single seam state

Structural highlights

8c0v is a 7 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 4.1Å
Ligands:	ADP, ATP, MG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PEX1_YEAST Component of the PEX1-PEX6 AAA ATPase complex, a protein dislocase complex that mediates the ATP-dependent extraction of the PEX5 receptor from peroxisomal membranes, an essential step for PEX5 recycling (PubMed:15634331, PubMed:16007078, PubMed:16911527, PubMed:26170309, PubMed:26066397, PubMed:29321502). Specifically recognizes PEX5 monoubiquitinated at 'Cys-6', and pulls it out of the peroxisome lumen through the PEX2-PEX10-PEX12 retrotranslocation channel (PubMed:26170309, PubMed:26066397, PubMed:29321502). Extraction by the PEX1-PEX6 AAA ATPase complex is accompanied by unfolding of the TPR repeats and release of bound cargo from PEX5 (PubMed:29321502).^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

The double-ring AAA+ ATPase Pex1/Pex6 is required for peroxisomal receptor recycling and is essential for peroxisome formation. Pex1/Pex6 mutations cause severe peroxisome associated developmental disorders. Despite its pathophysiological importance, mechanistic details of the heterohexamer are not yet available. Here, we report cryoEM structures of Pex1/Pex6 from Saccharomyces cerevisiae, with an endogenous protein substrate trapped in the central pore of the catalytically active second ring (D2). Pairs of Pex1/Pex6(D2) subdomains engage the substrate via a staircase of pore-1 loops with distinct properties. The first ring (D1) is catalytically inactive but undergoes significant conformational changes resulting in alternate widening and narrowing of its pore. These events are fueled by ATP hydrolysis in the D2 ring and disengagement of a "twin-seam" Pex1/Pex6(D2) heterodimer from the staircase. Mechanical forces are propagated in a unique manner along Pex1/Pex6 interfaces that are not available in homo-oligomeric AAA-ATPases. Our structural analysis reveals the mechanisms of how Pex1 and Pex6 coordinate to achieve substrate translocation.

Structure of the peroxisomal Pex1/Pex6 ATPase complex bound to a substrate.,Ruttermann M, Koci M, Lill P, Geladas ED, Kaschani F, Klink BU, Erdmann R, Gatsogiannis C Nat Commun. 2023 Sep 23;14(1):5942. doi: 10.1038/s41467-023-41640-9. PMID:37741838^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Birschmann I, Rosenkranz K, Erdmann R, Kunau WH. Structural and functional analysis of the interaction of the AAA-peroxins Pex1p and Pex6p. FEBS J. 2005 Jan;272(1):47-58. PMID:15634331 doi:10.1111/j.1432-1033.2004.04393.x
↑ Platta HW, Grunau S, Rosenkranz K, Girzalsky W, Erdmann R. Functional role of the AAA peroxins in dislocation of the cycling PTS1 receptor back to the cytosol. Nat Cell Biol. 2005 Aug;7(8):817-22. PMID:16007078 doi:10.1038/ncb1281
↑ Rosenkranz K, Birschmann I, Grunau S, Girzalsky W, Kunau WH, Erdmann R. Functional association of the AAA complex and the peroxisomal importomer. FEBS J. 2006 Aug;273(16):3804-15. PMID:16911527 doi:10.1111/j.1742-4658.2006.05388.x
↑ Ciniawsky S, Grimm I, Saffian D, Girzalsky W, Erdmann R, Wendler P. Molecular snapshots of the Pex1/6 AAA+ complex in action. Nat Commun. 2015 Jun 12;6:7331. PMID:26066397 doi:10.1038/ncomms8331
↑ Blok NB, Tan D, Wang RY, Penczek PA, Baker D, DiMaio F, Rapoport TA, Walz T. Unique double-ring structure of the peroxisomal Pex1/Pex6 ATPase complex revealed by cryo-electron microscopy. Proc Natl Acad Sci U S A. 2015 Jul 28;112(30):E4017-25. PMID:26170309 doi:10.1073/pnas.1500257112
↑ Gardner BM, Castanzo DT, Chowdhury S, Stjepanovic G, Stefely MS, Hurley JH, Lander GC, Martin A. The peroxisomal AAA-ATPase Pex1/Pex6 unfolds substrates by processive threading. Nat Commun. 2018 Jan 10;9(1):135. doi: 10.1038/s41467-017-02474-4. PMID:29321502 doi:https://dx.doi.org/10.1038/s41467-017-02474-4
↑ Rüttermann M, Koci M, Lill P, Geladas ED, Kaschani F, Klink BU, Erdmann R, Gatsogiannis C. Structure of the peroxisomal Pex1/Pex6 ATPase complex bound to a substrate. Nat Commun. 2023 Sep 23;14(1):5942. PMID:37741838 doi:10.1038/s41467-023-41640-9

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OCA

[1] Birschmann I, Rosenkranz K, Erdmann R, Kunau WH. Structural and functional analysis of the interaction of the AAA-peroxins Pex1p and Pex6p. FEBS J. 2005 Jan;272(1):47-58. PMID:15634331 doi:10.1111/j.1432-1033.2004.04393.x

[2] Platta HW, Grunau S, Rosenkranz K, Girzalsky W, Erdmann R. Functional role of the AAA peroxins in dislocation of the cycling PTS1 receptor back to the cytosol. Nat Cell Biol. 2005 Aug;7(8):817-22. PMID:16007078 doi:10.1038/ncb1281

[3] Rosenkranz K, Birschmann I, Grunau S, Girzalsky W, Kunau WH, Erdmann R. Functional association of the AAA complex and the peroxisomal importomer. FEBS J. 2006 Aug;273(16):3804-15. PMID:16911527 doi:10.1111/j.1742-4658.2006.05388.x

[4] Ciniawsky S, Grimm I, Saffian D, Girzalsky W, Erdmann R, Wendler P. Molecular snapshots of the Pex1/6 AAA+ complex in action. Nat Commun. 2015 Jun 12;6:7331. PMID:26066397 doi:10.1038/ncomms8331

[5] Blok NB, Tan D, Wang RY, Penczek PA, Baker D, DiMaio F, Rapoport TA, Walz T. Unique double-ring structure of the peroxisomal Pex1/Pex6 ATPase complex revealed by cryo-electron microscopy. Proc Natl Acad Sci U S A. 2015 Jul 28;112(30):E4017-25. PMID:26170309 doi:10.1073/pnas.1500257112

[6] Gardner BM, Castanzo DT, Chowdhury S, Stjepanovic G, Stefely MS, Hurley JH, Lander GC, Martin A. The peroxisomal AAA-ATPase Pex1/Pex6 unfolds substrates by processive threading. Nat Commun. 2018 Jan 10;9(1):135. doi: 10.1038/s41467-017-02474-4. PMID:29321502 doi:https://dx.doi.org/10.1038/s41467-017-02474-4

[7] Rüttermann M, Koci M, Lill P, Geladas ED, Kaschani F, Klink BU, Erdmann R, Gatsogiannis C. Structure of the peroxisomal Pex1/Pex6 ATPase complex bound to a substrate. Nat Commun. 2023 Sep 23;14(1):5942. PMID:37741838 doi:10.1038/s41467-023-41640-9

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8c0v | pdb_00008c0v

Structure of the peroxisomal Pex1/Pex6 ATPase complex bound to a substrate in single seam state

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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