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

Linear motifs regulating protein secretion, sorting and autophagy in Leishmania parasites are diverged with respect to their host equivalents

“…cerevisiae and A . thaliana ) featured on LIRcentral [ 61 ], we found that this strict definition still recovers 48% of all known functional LIR motifs (and all core autophagy apparatus motifs), while rejecting 78% of non-functional ones ( S20 Table ). However, even with these restrictions, the number of motif hits in Leishmania proteomes were still very large.…”

The LC3-interacting region of NBR1 is a protein interaction hub enabling optimal flux

“…Sequences were obtained from Uniprot and the LIR-central database (Chatzichristofi et al ., 2023). AF2-multimer was used with MMseqs2 through Google Colab ( htps://colab.…”

“…Peptides arrays were printed by the MIT Biopolymers & Proteomics Core. LIR sequences were drawn from the LIR-Central database (Chatzichristofi et al ., 2023) ( Supplemental Table 1 ). FIR sequences were drawn from (Fujita et al ., 2013; Smith et al ., 2018; Ravenhill et al ., 2019; Fu et al ., 2021; Zhou et al ., 2021).…”

“…Moreover, our demonstration of TAX1BP1 binding in relation to a LIR and FIR prompts an additional question: do LIRs or FIRs also bind TAX1BP1? To answer these questions, we printed a peptide array comprising 100 established LIR sequences from the LIR-Central database (Chatzichristofi et al, 2023) (Supplemental Table 1). As a control, we included the multifunctional NBR1 725-749 sequence identified in Fig 1B . We also included 5 previously reported FIR peptides as a control for FIP200 binding (Fujita et al, 2013;Smith et al, 2018;Ravenhill et al, 2019;Fu et al, 2021;Zhou et al, 2021).…”

“…Pep�des arrays were printed by the MIT Biopolymers & Proteomics Core. LIR sequences were drawn from the LIR-Central database (Chatzichristofi et al, 2023) (Supplemental Table 1).…”