title: Ego3 functions as a homodimer to mediate the interaction between Gtr1-Gtr2 and Ego1 in the ego complex to activate TORC1.
abstract: The yeast EGO complex, consisting of Gtr1, Gtr2, Ego1, and Ego3, localizes to the endosomal and vacuolar membranes and plays a pivotal role in cell growth and autophagy regulation through relaying amino acid signals to activate TORC1. Here, we report the crystal structures of a wild-type and a mutant form of Saccharomyces cerevisiae Ego3. Ego3 assumes a homodimeric structure similar to that of the mammalian MP1-p14 heterodimer and the C-terminal domains of the yeast Gtr1-Gtr2 heterodimer, both of which function in TORC1 signaling. Structural and genetic data demonstrate that the unique dimer conformation of Ego3 is essential for the integrity and function of the EGO complex. Structural and functional data also identify a potential binding site for Gtr1-Gtr2. These results suggest a structural conservation of the protein components involved in amino acid signaling to TORC1 and reveal structural insights into the molecular mechanism of Ego3 function in TORC1 signaling.
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Tianlong
authors.initials: T
authors.lastname: Zhang
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Péli-Gulli
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Claudio
authors.initials: C
authors.lastname: De Virgilio
authors.forename: Jianping
authors.initials: J
authors.lastname: Ding
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001665:Binding Sites; D018360:Crystallography, X-Ray; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D040681:Structural Homology, Protein; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C121263:GTR2 protein, S cerevisiae; C552591:Gse1 protein, S cerevisiae; C121262:Gtr1 protein, S cerevisiae; C501979:MEH1 protein, S cerevisiae; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; C561842:TORC1 protein complex, S cerevisiae; D014157:Transcription Factors; D020559:Monomeric GTP-Binding Proteins