5JM6

Structure of Chaetomium thermophilum mApe1

Summary for 5JM6

• Entry DOI: 10.2210/pdb5jm6/pdb
• Descriptor: Aminopeptidase-like protein, ZINC ION (3 entities in total)
• Functional Keywords: aminopeptidase, dodecamer, cvt pathway, selective autophagy, hydrolase
• Biological source: Chaetomium thermophilum
• Total number of polymer chains: 6
• Total formula weight: 339187.63

Authors

Bertipaglia, C.,Jakobi, A.J.,Wilmanns, M.,Sachse, C. (deposition date: 2016-04-28, release date: 2016-06-15, Last modification date: 2024-01-10)

Primary citation

Bertipaglia, C.,Schneider, S.,Jakobi, A.J.,Tarafder, A.K.,Bykov, Y.S.,Picco, A.,Kukulski, W.,Kosinski, J.,Hagen, W.J.,Ravichandran, A.C.,Wilmanns, M.,Kaksonen, M.,Briggs, J.A.,Sachse, C.
Higher-order assemblies of oligomeric cargo receptor complexes form the membrane scaffold of the Cvt vesicle.
Embo Rep., 17:1044-1060, 2016

PubMed Abstract: Selective autophagy is the mechanism by which large cargos are specifically sequestered for degradation. The structural details of cargo and receptor assembly giving rise to autophagic vesicles remain to be elucidated. We utilize the yeast cytoplasm-to-vacuole targeting (Cvt) pathway, a prototype of selective autophagy, together with a multi-scale analysis approach to study the molecular structure of Cvt vesicles. We report the oligomeric nature of the major Cvt cargo Ape1 with a combined 2.8 Å X-ray and negative stain EM structure, as well as the secondary cargo Ams1 with a 6.3 Å cryo-EM structure. We show that the major dodecameric cargo prApe1 exhibits a tendency to form higher-order chain structures that are broken upon interaction with the receptor Atg19 in vitro The stoichiometry of these cargo-receptor complexes is key to maintaining the size of the Cvt aggregate in vivo Using correlative light and electron microscopy, we further visualize key stages of Cvt vesicle biogenesis. Our findings suggest that Atg19 interaction limits Ape1 aggregate size while serving as a vehicle for vacuolar delivery of tetrameric Ams1.

PubMed: 27266708
DOI: 10.15252/embr.201541960

Experimental method

X-RAY DIFFRACTION (2.758 Å)