6WR4

Structure of human ATG9A, the only transmembrane protein of the core autophagy machinery

Summary for 6WR4

• Entry DOI: 10.2210/pdb6wr4/pdb
• EMDB information: 21874 21876 21877 21878
• Descriptor: Autophagy-related protein 9A, Lauryl Maltose Neopentyl Glycol (2 entities in total)
• Functional Keywords: tg9a, autophagosome, autophagy, cryoem, molecular dynamics, transmembrane protein, membranecurvature, cellular compartments, membrane morphology, lipids, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 3
• Total formula weight: 289684.22

Authors

Guardia, C.M.,Tan, X.,Lian, T.,Rana, M.S.,Zhou, W.,Christenson, E.T.,Lowry, A.J.,Faraldo-Gomez, J.D.,Bonifacino, J.S.,Jiang, J.,Banerjee, A. (deposition date: 2020-04-29, release date: 2020-07-08, Last modification date: 2024-03-06)

Primary citation

Guardia, C.M.,Tan, X.F.,Lian, T.,Rana, M.S.,Zhou, W.,Christenson, E.T.,Lowry, A.J.,Faraldo-Gomez, J.D.,Bonifacino, J.S.,Jiang, J.,Banerjee, A.
Structure of Human ATG9A, the Only Transmembrane Protein of the Core Autophagy Machinery.
Cell Rep, 31:107837-107837, 2020

PubMed Abstract: Autophagy is a catabolic process involving capture of cytoplasmic materials into double-membraned autophagosomes that subsequently fuse with lysosomes for degradation of the materials by lysosomal hydrolases. One of the least understood components of the autophagy machinery is the transmembrane protein ATG9. Here, we report a cryoelectron microscopy structure of the human ATG9A isoform at 2.9-Å resolution. The structure reveals a fold with a homotrimeric domain-swapped architecture, multiple membrane spans, and a network of branched cavities, consistent with ATG9A being a membrane transporter. Mutational analyses support a role for the cavities in the function of ATG9A. In addition, structure-guided molecular simulations predict that ATG9A causes membrane bending, explaining the localization of this protein to small vesicles and highly curved edges of growing autophagosomes.

PubMed: 32610138
DOI: 10.1016/j.celrep.2020.107837

Experimental method

ELECTRON MICROSCOPY (2.9 Å)