title: The crystal structure of mouse LC3B in complex with the FYCO1 LIR reveals the importance of the flanking region of the LIR motif.
abstract: FYVE and coiled-coil domain-containing protein 1 (FYCO1), a multidomain autophagy adaptor protein, mediates microtubule plus-end-directed autophagosome transport by interacting with kinesin motor proteins and with the autophagosomal membrane components microtubule-associated protein 1 light chain 3 (LC3), Rab7 and phosphatidylinositol 3-phosphate (PI3P). To establish the structural basis for the recognition of FYCO1 by LC3, the crystal structure of mouse LC3B in complex with the FYCO1 LC3-interacting region (LIR) motif peptide was determined. Structural analysis showed that the flanking sequences N-terminal and C-terminal to the LIR core sequence of FYCO1, as well as the tetrapeptide core sequence, were specifically recognized by LC3B and contributed to the binding. Moreover, comparisons of related structures revealed a conserved mechanism of FYCO1 recognition by different LC3 isoforms among different species.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Shunya
authors.initials: S
authors.lastname: Sakurai
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Tomita
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Umeharu
authors.initials: U
authors.lastname: Ohto
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: C000625145:FYCO1 protein, mouse; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors
keywords: FYCO1; LC3; LC3-interacting region (LIR) motif; autophagy