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4r8f

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Revision as of 16:08, 17 May 2017

Crystal structure of yeast aminopeptidase 1 (Ape1)

Structural highlights

4r8f is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Activity:	Aminopeptidase I, with EC number 3.4.11.22
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

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^[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Leber R, Silles E, Sandoval IV, Mazon MJ. Yol082p, a novel CVT protein involved in the selective targeting of aminopeptidase I to the yeast vacuole. J Biol Chem. 2001 Aug 3;276(31):29210-7. Epub 2001 May 29. PMID:11382752 doi:http://dx.doi.org/10.1074/jbc.M101438200
↑ Scott SV, Guan J, Hutchins MU, Kim J, Klionsky DJ. Cvt19 is a receptor for the cytoplasm-to-vacuole targeting pathway. Mol Cell. 2001 Jun;7(6):1131-41. PMID:11430817
↑ Shintani T, Klionsky DJ. Cargo proteins facilitate the formation of transport vesicles in the cytoplasm to vacuole targeting pathway. J Biol Chem. 2004 Jul 16;279(29):29889-94. Epub 2004 May 11. PMID:15138258 doi:http://dx.doi.org/10.1074/jbc.M404399200
↑ Morales Quinones M, Winston JT, Stromhaug PE. Propeptide of aminopeptidase 1 protein mediates aggregation and vesicle formation in cytoplasm-to-vacuole targeting pathway. J Biol Chem. 2012 Mar 23;287(13):10121-33. doi: 10.1074/jbc.M111.311696. Epub, 2011 Nov 28. PMID:22123825 doi:http://dx.doi.org/10.1074/jbc.M111.311696
↑ Frey J, Rohm KH. Subcellular localization and levels of aminopeptidases and dipeptidase in Saccharomyces cerevisiae. Biochim Biophys Acta. 1978 Nov 10;527(1):31-41. PMID:363165
↑ Scott SV, Hefner-Gravink A, Morano KA, Noda T, Ohsumi Y, Klionsky DJ. Cytoplasm-to-vacuole targeting and autophagy employ the same machinery to deliver proteins to the yeast vacuole. Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12304-8. PMID:8901576
↑ Scott SV, Baba M, Ohsumi Y, Klionsky DJ. Aminopeptidase I is targeted to the vacuole by a nonclassical vesicular mechanism. J Cell Biol. 1997 Jul 14;138(1):37-44. PMID:9214379
↑ Baba M, Osumi M, Scott SV, Klionsky DJ, Ohsumi Y. Two distinct pathways for targeting proteins from the cytoplasm to the vacuole/lysosome. J Cell Biol. 1997 Dec 29;139(7):1687-95. PMID:9412464
↑ Su MY, Peng WH, Ho MR, Su SC, Chang YC, Chen GC, Chang CI. Structure of yeast Ape1 and its role in autophagic vesicle formation. Autophagy. 2015 Jul 24:0. PMID:26208681 doi:http://dx.doi.org/10.1080/15548627.2015.1067363

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4r8f"

@@ Line 1: / Line 1: @@
 ==Crystal structure of yeast aminopeptidase 1 (Ape1)==
 <StructureSection load='4r8f' size='340' side='right' caption='[[4r8f]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4r8f]] is a 4 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R8F FirstGlance]. <br>
 </td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aminopeptidase_I Aminopeptidase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.11.22 3.4.11.22] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4r8f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r8f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4r8f RCSB], [http://www.ebi.ac.uk/pdbsum/4r8f PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4r8f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r8f OCA], [http://pdbe.org/4r8f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r8f RCSB], [http://www.ebi.ac.uk/pdbsum/4r8f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r8f ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4r8f" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Aminopeptidase|Aminopeptidase]]
 == References ==
 <references/>

4r8f

From Proteopedia

Revision as of 16:08, 17 May 2017

Crystal structure of yeast aminopeptidase 1 (Ape1)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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