title: hfAIM: A reliable bioinformatics approach for in silico genome-wide identification of autophagy-associated Atg8-interacting motifs in various organisms.
abstract: Most of the proteins that are specifically turned over by selective autophagy are recognized by the presence of short Atg8 interacting motifs (AIMs) that facilitate their association with the autophagy apparatus. Such AIMs can be identified by bioinformatics methods based on their defined degenerate consensus F/W/Y-X-X-L/I/V sequences in which X represents any amino acid. Achieving reliability and/or fidelity of the prediction of such AIMs on a genome-wide scale represents a major challenge. Here, we present a bioinformatics approach, high fidelity AIM (hfAIM), which uses additional sequence requirements-the presence of acidic amino acids and the absence of positively charged amino acids in certain positions-to reliably identify AIMs in proteins. We demonstrate that the use of the hfAIM method allows for in silico high fidelity prediction of AIMs in AIM-containing proteins (ACPs) on a genome-wide scale in various organisms. Furthermore, by using hfAIM to identify putative AIMs in the Arabidopsis proteome, we illustrate a potential contribution of selective autophagy to various biological processes. More specifically, we identified 9 peroxisomal PEX proteins that contain hfAIM motifs, among which AtPEX1, AtPEX6 and AtPEX10 possess evolutionary-conserved AIMs. Bimolecular fluorescence complementation (BiFC) results verified that AtPEX6 and AtPEX10 indeed interact with Atg8 in planta. In addition, we show that mutations occurring within or nearby hfAIMs in PEX1, PEX6 and PEX10 caused defects in the growth and development of various organisms. Taken together, the above results suggest that the hfAIM tool can be used to effectively perform genome-wide in silico screens of proteins that are potentially regulated by selective autophagy. The hfAIM system is a web tool that can be accessed at link: http://bioinformatics.psb.ugent.be/hfAIM/.
authors.affiliation: a Department of Plant and Environmental Science , Weizmann Institute of Science , Rehovotx , Israel.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Xie
authors.affiliation: a Department of Plant and Environmental Science , Weizmann Institute of Science , Rehovotx , Israel.|b Department of Plant Systems Biology , VIB , Ghent , Belgium.|c Department of Plant Biotechnology and Bioinformatics , Ghent University , Ghent , Belgium.|d Bioinformatics Institute Ghent, Ghent University , Ghent , Belgium.
authors.forename: Oren
authors.initials: O
authors.lastname: Tzfadia
authors.affiliation: a Department of Plant and Environmental Science , Weizmann Institute of Science , Rehovotx , Israel.
authors.forename: Matan
authors.initials: M
authors.lastname: Levy
authors.affiliation: a Department of Plant and Environmental Science , Weizmann Institute of Science , Rehovotx , Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Weithorn
authors.affiliation: a Department of Plant and Environmental Science , Weizmann Institute of Science , Rehovotx , Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Peled-Zehavi
authors.affiliation: b Department of Plant Systems Biology , VIB , Ghent , Belgium.|c Department of Plant Biotechnology and Bioinformatics , Ghent University , Ghent , Belgium.|d Bioinformatics Institute Ghent, Ghent University , Ghent , Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Van Parys
authors.affiliation: b Department of Plant Systems Biology , VIB , Ghent , Belgium.|c Department of Plant Biotechnology and Bioinformatics , Ghent University , Ghent , Belgium.|d Bioinformatics Institute Ghent, Ghent University , Ghent , Belgium.|e Genomics Research Institute (GRI), University of Pretoria , Pretoria , South Africa.
authors.forename: Yves
authors.initials: Y
authors.lastname: Van de Peer
authors.affiliation: a Department of Plant and Environmental Science , Weizmann Institute of Science , Rehovotx , Israel.
authors.forename: Gad
authors.initials: G
authors.lastname: Galili
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D017360:Arabidopsis / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D000071190:Autophagy-Related Protein 8 Family / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D016681:Genome, Fungal; D018745:Genome, Plant; D000072417:Protein Domains / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071190:Autophagy-Related Protein 8 Family; D029701:Saccharomyces cerevisiae Proteins
keywords: AIM; Arabidopsis; Atg8; PEX; autophagy; bioinformatics; pexophagy