The peroxisomal AAA-ATPase Pex1/Pex6 unfolds substrates by processive threading [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 572.6 Proteins
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2018
• Mô tả vật lý: Size: Article No. 135 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 260289
• Chủ đề: 1. 59 basic biological sciences; 2. 60 applied life sciences; 3. Electron microscopy; 4. Enzyme mechanisms; 5. Mechanisms of disease; 6. Peroxisomes; 7. Science & technology - other topics; 8. X-ray crystallography

Tóm tắt

Pex1 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.