4R8F
Crystal structure of yeast aminopeptidase 1 (Ape1)
Summary for 4R8F
| Entry DOI | 10.2210/pdb4r8f/pdb |
| Descriptor | Vacuolar aminopeptidase 1 (2 entities in total) |
| Functional Keywords | peptidase, cvt pathway, autophagy, hydrolase |
| Biological source | Saccharomyces cerevisiae S288c (yeast) |
| Cellular location | Vacuole : P14904 |
| Total number of polymer chains | 4 |
| Total formula weight | 207546.06 |
| Authors | Su, M.-Y.,Chang, C.-I. (deposition date: 2014-09-02, release date: 2015-08-12, Last modification date: 2023-11-08) |
| Primary citation | Su, M.Y.,Peng, W.H.,Ho, M.R.,Su, S.C.,Chang, Y.C.,Chen, G.C.,Chang, C.I. Structure of yeast Ape1 and its role in autophagic vesicle formation. Autophagy, 11:1580-1593, 2015 Cited by PubMed Abstract: In Saccharomyces cerevisiae, a constitutive biosynthetic transport pathway, termed the cytoplasm-to-vacuole targeting (Cvt) pathway, sequesters precursor aminopeptidase I (prApe1) dodecamers in the form of a large complex into a Cvt vesicle using autophagic machinery, targeting it into the vacuole (the yeast lysosome) where it is proteolytically processed into its mature form, Ape1, by removal of an amino-terminal 45-amino acid propeptide. prApe1 is thought to serve as a scaffolding cargo critical for the assembly of the Cvt vesicle by presenting the propeptide to mediate higher-ordered complex formation and autophagic receptor recognition. Here we report the X-ray crystal structure of Ape1 at 2.5 Å resolution and reveal its dodecameric architecture consisting of dimeric and trimeric units, which associate to form a large tetrahedron. The propeptide of prApe1 exhibits concentration-dependent oligomerization and forms a stable tetramer. Structure-based mutagenesis demonstrates that disruption of the inter-subunit interface prevents dodecameric assembly and vacuolar targeting in vivo despite the presence of the propeptide. Furthermore, by examining the vacuolar import of propeptide-fused exogenous protein assemblies with different quaternary structures, we found that 3-dimensional spatial distribution of propeptides presented by a scaffolding cargo is essential for the assembly of the Cvt vesicle for vacuolar delivery. This study describes a molecular framework for understanding the mechanism of Cvt or autophagosomal biogenesis in selective macroautophagy. PubMed: 26208681DOI: 10.1080/15548627.2015.1067363 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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