4r8f: Difference between revisions
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==Crystal structure of yeast aminopeptidase 1 (Ape1)== | ==Crystal structure of yeast aminopeptidase 1 (Ape1)== | ||
<StructureSection load='4r8f' size='340' side='right'caption='[[4r8f]]' scene=''> | <StructureSection load='4r8f' size='340' side='right'caption='[[4r8f]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R8F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R8F FirstGlance]. <br> | <table><tr><td colspan='2'>[[4r8f]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R8F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R8F FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4r8f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r8f OCA], [https://pdbe.org/4r8f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r8f RCSB], [https://www.ebi.ac.uk/pdbsum/4r8f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r8f ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4r8f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r8f OCA], [https://pdbe.org/4r8f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r8f RCSB], [https://www.ebi.ac.uk/pdbsum/4r8f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r8f ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/AMPL_YEAST AMPL_YEAST] Resident vacuolar enzyme that catalyzes the removal of amino acids from the N-terminus of peptides and proteins. Also acts as the major cargo protein of the cytoplasm-to-vacuole targeting (Cvt) pathway. The precursor form of aminopeptidase 1 (prApe1) assembles into dodecamers and the propeptide mediates the aggregation of dodecamers into higher multimers. The multimers are then recognized via the propeptide by their receptor ATG19, and ATG19 further interacts with ATG11, which tethers the APE1-ATG19 complex to the pre-autophagosomal structure (PAS). The cargo-receptor complex (also Cvt complex) is selectively enwrapped by a double-membrane structure termed the Cvt vesicle under vegetative growth conditions and by a similar but larger double-membrane structure termed the autophagosome under nitrogen starvation conditions. The Cvt vesicle or the autophagosome fuses with the vacuolar membrane and release its content in the vacuolar lumen. In the vacuole, prApe1 is processed into mature aminopeptidase 1 (mApe1).<ref>PMID:11382752</ref> <ref>PMID:11430817</ref> <ref>PMID:15138258</ref> <ref>PMID:22123825</ref> <ref>PMID:363165</ref> <ref>PMID:8901576</ref> <ref>PMID:9214379</ref> <ref>PMID:9412464</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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 A 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. | |||
Structure of yeast Ape1 and its role in autophagic vesicle formation.,Su MY, Peng WH, Ho MR, Su SC, Chang YC, Chen GC, Chang CI Autophagy. 2015 Jul 24:0. PMID:26208681<ref>PMID:26208681</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4r8f" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]] | *[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Saccharomyces cerevisiae S288C]] | |||
[[Category: Chang C-I]] | [[Category: Chang C-I]] | ||
[[Category: Su M-Y]] | [[Category: Su M-Y]] | ||