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

J. Biol. Chem., Vol. 280, Issue 26, 24610-24617, July 1, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/26/24610    most recent M413565200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Kouno, T. Articles by Kawano, K. Search for Related Content PubMed PubMed Citation Articles by Kouno, T. Articles by Kawano, K. Social Bookmarking                      What's this?

Solution Structure of Microtubule-associated Protein Light Chain 3 and Identification of Its Functional Subdomains^*

Takahide Kouno, Mineyuki Mizuguchi, Isei Tanida¶, Takashi Ueno¶, Takashi Kanematsu||, Yoshihiro Mori, Hiroyuki Shinoda, Masato Hirata||, Eiki Kominami¶, and Keiichi Kawano**

From the Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan, the ^¶Department of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan, the ^||Faculty of Dental Sciences and Station for Collaborative Research, Kyushu University, Fukuoka 812-8582, Japan, and the ^**Division of Biological Sciences, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan

Microtubule-associated protein (MAP) light chain 3 (LC3) is a human homologue of yeast Apg8/Aut7/Cvt5 (Atg8), which is essential for autophagy. MAP-LC3 is cleaved by a cysteine protease to produce LC3-I, which is located in cytosolic fraction. LC3-I, in turn, is converted to LC3-II through the actions of E1- and E2-like enzymes. LC3-II is covalently attached to phosphatidylethanolamine on its C terminus, and it binds tightly to autophagosome membranes. We determined the solution structure of LC3-I and found that it is divided into N- and C-terminal subdomains. Additional analysis using a photochemically induced dynamic nuclear polarization technique also showed that the N-terminal subdomain of LC3-I makes contact with the surface of the C-terminal subdomain and that LC3-I adopts a single compact conformation in solution. Moreover, the addition of dodecylphosphocholine into the LC3-I solution induced chemical shift perturbations primarily in the C-terminal subdomain, which implies that the two subdomains have different sensitivities to dodecylphosphocholine micelles. On the other hand, deletion of the N-terminal subdomain abolished binding of tubulin and microtubules. Thus, we showed that two subdomains of the LC3-I structure have distinct functions, suggesting that MAP-LC3 can act as an adaptor protein between microtubules and autophagosomes.

Received for publication, December 2, 2004 , and in revised form, March 28, 2005.

Note Added in Proof—The crystal structute of rat MAP-LC3 was independently reported by Sugawara et al. (62).

^* This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Program for the Promotion of Basic Research Activities for Innovative Biosciences (Japan), the National Project on Protein Structural and Functional Analyses (Japan), and by a grant from the Ministry of Agriculture, Forestry, and Fisheries of Japan, Rice Genome Project PR-4101. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The atomic coordinates and structure factors (code 1V49) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

To whom correspondence may be addressed: Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan. Tel.: 81-76-434-7595; Fax: 81-76-434-5061; E-mail: mineyuki{at}ms.toyama-mpu.ac.jp. To whom correspondence may be addressed: Division of Biological Sciences, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan. Tel./Fax: 81-11-706-4993; E-mail: kawano{at}sci.hokudai.ac.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				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]

				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]

				A. Simonsen, R. C. Cumming, K. Lindmo, V. Galaviz, S. Cheng, T. E. Rusten, and K. D. Finley Genetic Modifiers of the Drosophila Blue Cheese Gene Link Defects in Lysosomal Transport With Decreased Life Span and Altered Ubiquitinated-Protein Profiles Genetics, June 1, 2007; 176(2): 1283 - 1297. [Abstract] [Full Text] [PDF]

				A. Abu, M. Frydman, D. Marek, E. Pras, C. Stolovitch, A. Aviram-Goldring, S. Rienstein, H. Reznik-Wolf, and E. Pras Mapping of a Gene Causing Brittle Cornea Syndrome in Tunisian Jews to 16q24 Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5283 - 5287. [Abstract] [Full Text] [PDF]

				B. P. Downes, S. A. Saracco, S. S. Lee, D. N. Crowell, and R. D. Vierstra MUBs, a Family of Ubiquitin-fold Proteins That Are Plasma Membrane-anchored by Prenylation J. Biol. Chem., September 15, 2006; 281(37): 27145 - 27157. [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]