The structure of human ATG9A and its interplay with the lipid bilayer. Issue 12 (1st December 2020)

• Record Type: Journal Article
• Authors: Guardia, Carlos M.; Christenson, Eric T.; Zhou, Wenchang; Tan, Xiao-Feng; Lian, Tengfei; Faraldo-Gómez, José D.; Bonifacino, Juan S.; Jiang, Jiansen; Banerjee, Anirban
• Is Part Of: Autophagy. Volume 16:Issue 12(2020)
• Page Start: 2292
• Page End: 2293
• Publication Date: 2020-12-01
• Subjects: ATG9A -- autophagosome -- cryo-EM -- membrane curvature -- molecular dynamics -- transmembrane protein; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2020.1830522
• Languages: English
• ISSNs: 1554-8627

Abstract

ABSTRACT: ATG9, the only transmembrane protein in the core macroautophagy/autophagy machinery, is a key player in the early stages of autophagosome formation. Yet, the lack of a high-resolution structure of ATG9 was a major impediment in understanding its three-dimensional organization and function. We recently solved a high-resolution cryoEM structure of the ubiquitously expressed human ATG9A isoform. The structure revealed that ATG9A is a domain-swapped homotrimer with a unique fold, and has an internal network of branched cavities. In cellulo analyses demonstrated the functional importance of the cavity-lining residues. These cavities could serve as conduits for transport of hydrophilic moieties, such as lipid headgroups, across the bilayer. Finally, structure-guided molecular dynamics predicted that ATG9A has membrane-bending properties, which is consistent with its localization to highly curved membranes.