title: Analysis of the native conformation of the LIR/AIM motif in the Atg8/LC3/GABARAP-binding proteins.
abstract: The Atg8/LC3/GABARAP family of proteins, a group that has structural homology with ubiquitin, connects with a large set of binding partners to function in macroautophagy (hereafter autophagy). This interaction occurs primarily via a conserved motif termed the LC3-interacting region (LIR), or the Atg8-interacting motif (AIM). The consensus sequence for this motif, [W/F/Y]xx[L/I/V], can be found in many proteins, but only some of them are physiological partners containing a functional LIR/AIM. Because the structure of many full-length partners has not been, or cannot be, solved, the structural context of the LIR/AIM within the native protein conformation is not obvious. Here we suggest that the functional LIR/AIM is a short linear motif (SLiM) protein-binding module, arising from an intrinsically disordered region. This finding enables the rapid elimination of some false Atg8/LC3/GABARAP-binding proteins, and connects the exponentially growing knowledge on disordered SLiMs with autophagy.
authors.affiliation: a Life Sciences Institute; University of Michigan ; Ann Arbor , MI USA.
authors.forename: Hana
authors.initials: H
authors.lastname: Popelka
authors.affiliation: a Life Sciences Institute; University of Michigan ; Ann Arbor , MI USA.|b Department of Molecular , Cellular, and Developmental Biology; University of Michigan ; Ann Arbor , MI USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Klionsky
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism; D020816:Amino Acid Motifs / Q000502:physiology; D000595:Amino Acid Sequence; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy / Q000502:physiology*; D000071190:Autophagy-Related Protein 8 Family; D002352:Carrier Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000071190:Autophagy-Related Protein 8 Family; D002352:Carrier Proteins; C116741:GABARAP protein, human; C498698:GABARAPL2 protein, human; C477012:MAP1LC3A protein, human; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins
keywords: AIM motif; Atg8; GABARAP; LC3; LIR motif; SLiM; intrinsic disorder