LIRcentral: a manually curated online database of experimentally validated functional LIR motifs

Abstract

Several selective macroautophagy receptor and adaptor proteins bind members of the Atg8 (autophagy related 8) family using short linear motifs (SLiMs), most often referred to as Atg8-family interacting motifs (AIMs) or LC3-interacting regions (LIRs). AIM/LIR motifs have been extensively studied during the last fifteen years, since they can uncover the underlying biological mechanisms and possible substrates for this key catabolic process of eukaryotic cells. Prompted by the fact that experimental information regarding LIR motifs can be found scattered across heterogeneous literature resources, we have developed LIRcentral (https://lircentral.eu), a freely available online repository for user-friendly access to comprehensive, high-quality information regarding LIR motifs from manually curated publications. Herein, we describe the development of LIRcentral and showcase currently available data and features, along with our plans for the expansion of this resource. Information incorporated in LIRcentral is useful for accomplishing a variety of research tasks, including: (i) guiding wet biology researchers for the characterization of novel instances of LIR motifs, (ii) giving bioinformaticians/computational biologists access to high-quality LIR motifs for building novel prediction methods for LIR motifs and LIR containing proteins (LIRCPs) and (iii) performing analyses to better understand the biological importance/features of functional LIR motifs. We welcome feedback on the LIRcentral content and functionality by all interested researchers and anticipate this work to spearhead a community effort for sustaining this resource which will further promote progress in studying LIR motifs/LIRCPs.Abbreviations: AIM, Atg8-family interacting motif; Atg8, autophagy related 8; GABARAP, GABA type A receptor-associated protein; LIR, LC3-interacting region; LIRCP, LIR-containing protein; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; PMID, PubMed identifier; PPI, protein-protein interaction; SLiM, short linear motif.

Keywords: Atg8 family; database; manual literature curation/annotation; online resource; peptide-protein interaction; selective macroautophagy.

Figure 1.

Word cloud representation of the textual content of all abstracts from the papers curated in the current LIRcentral version (left) versus 1000 articles retrieved by the keyword “autophagy” using the Bio:Entrez module of Biopython (right).

Figure 2.

A Venn diagram representation of the overlaps between different literature collections related to LIR motifs. Drawn using https://bioinformatics.psb.ugent.be/webtools/Venn/.

Figure 3.

Distribution of publication dates for manuscripts describing experimentally verified LIR motifs in the current version of LIRcentral and comparison to other literature collections of LIR motifs.

Figure 4.

The LIRcentral landing page (“Home”). It provides a short introduction to the purpose of LIRcentral with a brief summary of the database content and links to all LIRcentral functionalities.

Figure 5.

Advanced search via the “Browse” functionality. Here all LIRcentral experimentally verified entries originating from species whose names match either “Toxoplasma” or “Plasmodium” are retrieved in a single query.

Figure 6.

Positional frequencies of different amino acid residue types for human experimentally verified functional (left; n = 101) and nonfunctional (right; n = 48) sequences matching the canonical LIR motif. Top: Logo-like representations; Bottom: Actual frequencies. Computations performed using PSSMsearch [36] using experimentally verified human LIR motif data retrieved from LIRcentral.

Figure 7.

PPI network using as input a list of 12 verified yeast LIRCP entries from LIRcentral. Proteins are represented as nodes while edges represent physical interactions between them. The input set was enhanced with the prediction of 20 additional entities based on known PPIs. Striped nodes signify input proteins and the color scheme corresponds to the top 5 gene ontology terms (FDR <10⁻¹²). This network was generated using the GeneMANIA web server https://genemania.org [42]: only yeast PPI data were used to infer 20 proteins related to the input dataset (all other parameters set to their default values).