8c0w

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

spinqualitylabelsall models 8c0w, resolution 4.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8c0w 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 4.7Å Ligands: ADP, ATP, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PEX6_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). 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA