Journal Article

PreJuSER-9748

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Solution structure of Atg8 reveals conformational polymorphism of the N-terminal domain

Schwarten, M. ; Stoldt, M. ; Mohrlüder, J.FZJ* ; Willbold, D.FZJ*

2010
Academic Press Orlando, Fla.

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Please use a persistent id in citations: doi:10.1016/j.bbrc.2010.04.043

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.

Keyword(s): Autophagy (MeSH) ; Microtubule-Associated Proteins: chemistry (MeSH) ; Nuclear Magnetic Resonance, Biomolecular (MeSH) ; Protein Folding (MeSH) ; Protein Structure, Tertiary (MeSH) ; Saccharomyces cerevisiae: chemistry (MeSH) ; Saccharomyces cerevisiae: physiology (MeSH) ; Saccharomyces cerevisiae Proteins: chemistry (MeSH) ; Ubiquitin: chemistry (MeSH) ; ATG8 protein, S cerevisiae ; Microtubule-Associated Proteins ; Saccharomyces cerevisiae Proteins ; Ubiquitin ; J ; Atg8 (auto) ; Autophagy (auto) ; NMR spectroscopy (auto) ; Dynamics (auto) ; GABARAP-like family (auto) ; Oligomerization (auto)

Note: We thank Sameer Singh for carefully reading the manuscript as well as Clara Gruning, Justin Lecher and Sven Schunke for helpful discussions. This study was supported by a fellowship of the International Helmholtz Research School of Biophysics and Soft Matter (IHRS BioSoft) to M. Schwarten and a research Grant from the Deutsche Forschungsgemeinschaft (DFG) to D. Willbold (Wi1472/5).

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Contributing Institute(s):

1. Strukturbiochemie (ISB-3)
2. Jülich Aachen Research Alliance - High-Performance Computing (JARA-HPC)

Research Program(s):

1. Funktion und Dysfunktion des Nervensystems (P33)
2. BioSoft: Makromolekulare Systeme und biologische Informationsverarbeitung (P45)

Appears in the scientific report 2010

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