PMID- 22123825
OWN - NLM
STAT- MEDLINE
DCOM- 20120516
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 287
IP  - 13
DP  - 2012 Mar 23
TI  - Propeptide of aminopeptidase 1 protein mediates aggregation and vesicle formation 
      in cytoplasm-to-vacuole targeting pathway.
PG  - 10121-10133
LID - S0021-9258(20)65425-4 [pii]
LID - 10.1074/jbc.M111.311696 [doi]
AB  - Misfolded protein aggregation causes disease and aging; autophagy counteracts 
      this by eliminating damaged components, enabling cells to survive starvation. The 
      cytoplasm-to-vacuole targeting pathway in yeast encompasses the aggregation of 
      the premature form of aminopeptidase 1 (prApe1) in cytosol and its sequestration 
      by autophagic proteins into a vesicle for vacuolar transport. We show that the 
      propeptide of Ape1 is important for aggregation and vesicle formation and that it 
      is sufficient for binding to prApe1 and Atg19. Defective aggregation disrupts 
      vacuolar transport, suggesting that aggregate shape is important in vesicle 
      formation, whereas Atg19 binding is not sufficient for vacuolar transport. 
      Aggregation involves hydrophobicity, whereas Atg19 binding requires additional 
      electrostatic interactions. Ape1 dodecamerization may cluster propeptides into 
      trimeric structures, with sufficient affinity to form propeptide hexamers by 
      binding to other dodecamers, causing aggregation. We show that Ape1 aggregates 
      bind Atg19 and Atg8 in vitro; this could be used as a scaffold for an in vitro 
      assay of autophagosome formation to elucidate the mechanisms of autophagy.
FAU - Morales Quinones, Mariana
AU  - Morales Quinones M
AD  - Department of Biological Sciences, University of Missouri, Columbia, Missouri 
      65211.
FAU - Winston, Jared T
AU  - Winston JT
AD  - Department of Biological Sciences, University of Missouri, Columbia, Missouri 
      65211.
FAU - Stromhaug, Per E
AU  - Stromhaug PE
AD  - Department of Biological Sciences, University of Missouri, Columbia, Missouri 
      65211. Electronic address: per@binghamton.edu.
LA  - eng
PT  - Journal Article
DEP - 20111128
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (ATG19 protein, S cerevisiae)
RN  - 0 (ATG8 protein, S cerevisiae)
RN  - 0 (Autophagy-Related Protein 8 Family)
RN  - 0 (Autophagy-Related Proteins)
RN  - 0 (Enzyme Precursors)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Vesicular Transport Proteins)
RN  - EC 3.4.11.- (Aminopeptidases)
RN  - EC 3.4.11.22 (APE1 protein, S cerevisiae)
SB  - IM
MH  - Aminopeptidases/genetics/*metabolism
MH  - Autophagy-Related Protein 8 Family
MH  - Autophagy-Related Proteins
MH  - Cytoplasm/*enzymology/genetics
MH  - Enzyme Precursors/genetics/*metabolism
MH  - Microtubule-Associated Proteins/genetics/metabolism
MH  - Protein Binding
MH  - Protein Multimerization/physiology
MH  - Receptors, Cell Surface/genetics/metabolism
MH  - Saccharomyces cerevisiae/*enzymology/genetics
MH  - Saccharomyces cerevisiae Proteins/genetics/*metabolism
MH  - Secretory Vesicles/*enzymology/genetics
MH  - Vacuoles/*enzymology/genetics
MH  - Vesicular Transport Proteins/genetics/metabolism
PMC - PMC3323037
EDAT- 2011/11/30 06:00
MHDA- 2012/05/17 06:00
PMCR- 2013/03/23
CRDT- 2011/11/30 06:00
PHST- 2011/11/30 06:00 [entrez]
PHST- 2011/11/30 06:00 [pubmed]
PHST- 2012/05/17 06:00 [medline]
PHST- 2013/03/23 00:00 [pmc-release]
AID - S0021-9258(20)65425-4 [pii]
AID - M111.311696 [pii]
AID - 10.1074/jbc.M111.311696 [doi]
PST - ppublish
SO  - J Biol Chem. 2012 Mar 23;287(13):10121-10133. doi: 10.1074/jbc.M111.311696. Epub 
      2011 Nov 28.