[PMID]: | 29321502 |
[Au] Autor: | Gardner BM; Castanzo DT; Chowdhury S; Stjepanovic G; Stefely MS; Hurley JH; Lander GC; Martin A |
[Ad] Endereço: | Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, 94720, USA. |
[Ti] Título: | The peroxisomal AAA-ATPase Pex1/Pex6 unfolds substrates by processive threading. |
[So] Source: | Nat Commun;9(1):135, 2018 01 10. |
[Is] ISSN: | 2041-1723 |
[Cp] País de publicação: | England |
[La] Idioma: | eng |
[Ab] Resumo: | 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. |
[Mh] Termos MeSH primário: |
ATPases Associadas a Diversas Atividades Celulares/metabolismo Proteínas de Membrana/metabolismo Peroxissomos/enzimologia Fosfoproteínas/metabolismo Proteínas de Saccharomyces cerevisiae/metabolismo
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[Mh] Termos MeSH secundário: |
Adenosina Trifosfatases/antagonistas & inibidores Conformação Proteica Saccharomyces cerevisiae
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S. |
[Nm] Nome de substância:
| 0 (Membrane Proteins); 0 (PEX15 protein, S cerevisiae); 0 (Phosphoproteins); 0 (Saccharomyces cerevisiae Proteins); EC 3.6.1.- (Adenosine Triphosphatases); EC 3.6.4.- (ATPases Associated with Diverse Cellular Activities); EC 3.6.4.- (PEX1 protein, S cerevisiae); EC 3.6.4.- (PEX6 protein, S cerevisiae) |
[Em] Mês de entrada: | 1802 |
[Cu] Atualização por classe: | 180212 |
[Lr] Data última revisão:
| 180212 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 180112 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1038/s41467-017-02474-4 |
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