HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE ADVANCED SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sugawara, K. Articles by Inagaki, F. Search for Related Content PubMed PubMed Citation Articles by Sugawara, K. Articles by Inagaki, F.

¹ Department of Structural Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan
² Department of Cell Biology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji, Okazaki 444-8585, Japan
³ Precursory Research for Embryonic Science and Technology (PREST), Japan Science and Technology Agency, Kawaguchi 332-0012, Japan

Microtubule-associated protein light chain 3 (LC3), a mammalian homologue of yeast Atg8, plays an essential role in autophagy, which is involved in the bulk degradation of cytoplasmic components by the lysosomal system. Here, we report the crystal structure of LC3 at 2.05 Å resolution with an R-factor of 21.8% and a free R-factor of 24.9%. The structure of LC3, which is similar to those of Golgi-associated ATPase enhancer of 16 kDa (GATE-16) and GABA_A receptor-associated protein (GABARAP), contains a ubiquitin core with two helices, 1 and 2, attached at its N-terminus. Some common and distinct features are observed among these proteins, including the conservation of residues required to form an interaction among 1, 2 and the ubiquitin core. However, the electrostatic potential surfaces of these helices differ, implicating particular roles to select specific binding partners. Hydrophobic patches on the ubiquitin core of LC3, GABARAP and GATE-16 are well conserved and are similar to the E1 binding surface of ubiquitin and NEDD8. Therefore, we propose that the hydrophobic patch is a binding surface for mammalian Atg7 similar to a ubiquitin-like conjugation system. We also propose the functional implications of the ubiquitin fold as a recognition module of target proteins.

^* Correspondence: E-mail: finagaki{at}pharm.hokudai.ac.jp

This article has been cited by other articles:

				N. N. Noda, H. Kumeta, H. Nakatogawa, K. Satoo, W. Adachi, J. Ishii, Y. Fujioka, Y. Ohsumi, and F. Inagaki Structural basis of target recognition by Atg8/LC3 during selective autophagy Genes Cells, December 1, 2008; 13(12): 1211 - 1218. [Abstract] [Full Text] [PDF]

				Y. Ichimura, T. Kumanomidou, Y.-s. Sou, T. Mizushima, J. Ezaki, T. Ueno, E. Kominami, T. Yamane, K. Tanaka, and M. Komatsu Structural Basis for Sorting Mechanism of p62 in Selective Autophagy J. Biol. Chem., August 15, 2008; 283(33): 22847 - 22857. [Abstract] [Full Text] [PDF]

				E. Shvets, E. Fass, R. Scherz-Shouval, and Z. Elazar The N-terminus and Phe52 residue of LC3 recruit p62/SQSTM1 into autophagosomes J. Cell Sci., August 15, 2008; 121(16): 2685 - 2695. [Abstract] [Full Text] [PDF]

				K. Oh-oka, H. Nakatogawa, and Y. Ohsumi Physiological pH and Acidic Phospholipids Contribute to Substrate Specificity in Lipidation of Atg8 J. Biol. Chem., August 8, 2008; 283(32): 21847 - 21852. [Abstract] [Full Text] [PDF]

				S. Pankiv, T. H. Clausen, T. Lamark, A. Brech, J.-A. Bruun, H. Outzen, A. Overvatn, G. Bjorkoy, and T. Johansen p62/SQSTM1 Binds Directly to Atg8/LC3 to Facilitate Degradation of Ubiquitinated Protein Aggregates by Autophagy J. Biol. Chem., August 17, 2007; 282(33): 24131 - 24145. [Abstract] [Full Text] [PDF]

				Y. Yamada, N. N. Suzuki, T. Hanada, Y. Ichimura, H. Kumeta, Y. Fujioka, Y. Ohsumi, and F. Inagaki The Crystal Structure of Atg3, an Autophagy-related Ubiquitin Carrier Protein (E2) Enzyme that Mediates Atg8 Lipidation J. Biol. Chem., March 16, 2007; 282(11): 8036 - 8043. [Abstract] [Full Text] [PDF]

				M. Matsushita, N. N. Suzuki, K. Obara, Y. Fujioka, Y. Ohsumi, and F. Inagaki Structure of Atg5{middle dot}Atg16, a Complex Essential for Autophagy J. Biol. Chem., March 2, 2007; 282(9): 6763 - 6772. [Abstract] [Full Text] [PDF]

				Y.-s. Sou, I. Tanida, M. Komatsu, T. Ueno, and E. Kominami Phosphatidylserine in Addition to Phosphatidylethanolamine Is an in Vitro Target of the Mammalian Atg8 Modifiers, LC3, GABARAP, and GATE-16 J. Biol. Chem., February 10, 2006; 281(6): 3017 - 3024. [Abstract] [Full Text] [PDF]

				K. Sugawara, N. N. Suzuki, Y. Fujioka, N. Mizushima, Y. Ohsumi, and F. Inagaki Structural Basis for the Specificity and Catalysis of Human Atg4B Responsible for Mammalian Autophagy J. Biol. Chem., December 2, 2005; 280(48): 40058 - 40065. [Abstract] [Full Text] [PDF]

				T. Kouno, M. Mizuguchi, I. Tanida, T. Ueno, T. Kanematsu, Y. Mori, H. Shinoda, M. Hirata, E. Kominami, and K. Kawano Solution Structure of Microtubule-associated Protein Light Chain 3 and Identification of Its Functional Subdomains J. Biol. Chem., July 1, 2005; 280(26): 24610 - 24617. [Abstract] [Full Text] [PDF]

				D. J. Klionsky The molecular machinery of autophagy: unanswered questions J. Cell Sci., January 1, 2005; 118(1): 7 - 18. [Abstract] [Full Text] [PDF]

				K. Yoshimoto, H. Hanaoka, S. Sato, T. Kato, S. Tabata, T. Noda, and Y. Ohsumi Processing of ATG8s, Ubiquitin-Like Proteins, and Their Deconjugation by ATG4s Are Essential for Plant Autophagy PLANT CELL, November 1, 2004; 16(11): 2967 - 2983. [Abstract] [Full Text] [PDF]

				Y. Ichimura, Y. Imamura, K. Emoto, M. Umeda, T. Noda, and Y. Ohsumi In Vivo and in Vitro Reconstitution of Atg8 Conjugation Essential for Autophagy J. Biol. Chem., September 24, 2004; 279(39): 40584 - 40592. [Abstract] [Full Text] [PDF]