title: Solution structure of Atg8 reveals conformational polymorphism of the N-terminal domain.
abstract: During autophagy a crescent shaped like membrane is formed, which engulfs the material that is to be degraded. This membrane grows further until its edges fuse to form the double membrane covered autophagosome. Atg8 is a protein, which is required for this initial step of autophagy. Therefore, a multistage conjugation process of newly synthesized Atg8 to phosphatidylethanolamine is of critical importance. Here we present the high resolution structure of unprocessed Atg8 determined by nuclear magnetic resonance spectroscopy. Its C-terminal subdomain shows a well-defined ubiquitin-like fold with slightly elevated mobility in the pico- to nanosecond timescale as determined by heteronuclear NOE data. In comparison to unprocessed Atg8, cleaved Atg8(G116) shows a decreased mobility behaviour. The N-terminal domain adopts different conformations within the micro- to millisecond timescale. The possible biological relevance of the differences in dynamic behaviours between both subdomains as well as between the cleaved and uncleaved forms is discussed.
authors.affiliation: Institut für Strukturbiologie und Biophysik, ISB-3, Forschungszentrum Jülich, 52425 Jülich, Germany. m.schwarten@fz-juelich.de
authors.forename: Melanie
authors.initials: M
authors.lastname: Schwarten
authors.forename: Matthias
authors.initials: M
authors.lastname: Stoldt
authors.forename: Jeannine
authors.initials: J
authors.lastname: Mohrlüder
authors.forename: Dieter
authors.initials: D
authors.lastname: Willbold
mesh_terms: D001343:Autophagy; D000071190:Autophagy-Related Protein 8 Family; D008869:Microtubule-Associated Proteins / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D025801:Ubiquitin / Q000737:chemistry
chemical_list: C113757:ATG8 protein, S cerevisiae; D000071190:Autophagy-Related Protein 8 Family; D008869:Microtubule-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin