Autophagy3D: a comprehensive autophagy structure database

Abstract

Autophagy pathway plays a central role in cellular degradation. The proteins involved in the core autophagy process are mostly localised on membranes or interact indirectly with lipid-associated proteins. Therefore, progress in structure determination of 'core autophagy proteins' remained relatively limited. Recent paradigm shift in structural biology that includes cutting-edge cryo-EM technology and robust AI-based Alphafold2 predicted models has significantly increased data points in biology. Here, we developed Autophagy3D, a web-based resource that provides an efficient way to access data associated with 40 core human autophagic proteins (80322 structures), their protein-protein interactors and ortholog structures from various species. Autophagy3D also offers detailed visualizations of protein structures, and, hence deriving direct biological insights. The database significantly enhances access to information as full datasets are available for download. The Autophagy3D can be publicly accessed via https://autophagy3d.igib.res.in. Database URL: https://autophagy3d.igib.res.in.

Figure 1.

The overview of the Autophagy3D database provides comprehensive structural data points associated with 40 core autophagy proteins, information about their interactions orthologs.

Figure 2.

The statistics of structural coverage in Autophagy3D for the segments (such as core-autophagic proteins, interactome of the core proteins, and the corresponding ortholog structures) are shown in the series of bar graphs.

Figure 3.

Structures of Autophagy3D database, where (a) shows the human autophagy proteins, where user can browse to human autophagy proteins using the browse button, (b) shows the available protein structures in monomeric, ligand bound and hetero-oligomer complex form on RCSB and AlphaFold database.

Figure 4.

Protein Structure result in Autophagy3D database, where (a) shows 3D view of the protein structure, providing different representation, coloring based on pLDDT score, screenshot, fullscreen, and download options.

Figure 5.

The interactome network is displayed on the webpage (a) The network is interactive and colored according to the availability of experimental structures, where on clicking a node (i.e. interactor), a new page gets opened on a new tab (b) shows the subpage of the interactor showcasing 3D-Visualisation space for the experimental structures of the interactor (AlphaFold model in case of non-availability).

Figure 6.

Orthologs in Autophagy3D database webpage displays MAP1LC3B metadata i.e. gene name, UniProt ID, sequence length, AlphaFold structure availability, pLDDT score etc., providing the facility to download the orthologs structures and its metadata.