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Structure. 2014 Jan 7;22(1):47-58. doi: 10.1016/j.str.2013.09.023. Epub 2013 Nov 27.

Structural basis of the autophagy-related LC3/Atg13 LIR complex: recognition and interaction mechanism.

Author information

1
Biomolecular Interaction Centre, School of Biological Sciences, University of Canterbury, Christchurch 8020, New Zealand; Structural Biology Research Center, Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), Tsukuba, Ibaraki 305-0801, Japan. Electronic address: hironori.suzuki@canterbury.ac.nz.
2
International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Department of Genetics, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
3
International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
4
Structural Biology Research Center, Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), Tsukuba, Ibaraki 305-0801, Japan.
5
Biomolecular Interaction Centre, School of Biological Sciences, University of Canterbury, Christchurch 8020, New Zealand; Department of Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address: renwick.dobson@canterbury.ac.nz.
6
Department of Genetics, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan; Laboratory of Intracellular Membrane Dynamics, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
7
Structural Biology Research Center, Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), Tsukuba, Ibaraki 305-0801, Japan; Photon Science, SLAC National Accelerator Laboratory, Menlo Park, CA 94025-7015, USA; Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305-5126, USA.

Abstract

Autophagy is a bulk degradation pathway that removes cytosolic materials to maintain cellular homeostasis. The autophagy-related gene 13 (Atg13) and microtubule associate protein 1 light chain 3 (LC3) proteins are required for autophagosome formation. We demonstrate that each of the human LC3 isoforms (LC3A, LC3B, and LC3C) interacts with Atg13 via the LC3 interacting region (LIR) of Atg13. Using X-ray crystallography, we solved the macromolecular structures of LC3A and LC3C, along with the complex structures of the LC3 isoforms with the Atg13 LIR. Together, our structural and binding analyses reveal that the side-chain of Lys49 of LC3 acts as a gatekeeper to regulate binding of the LIR. We verified this observation by mutation of Lys49 in LC3A, which significantly reduces LC3A positive puncta formation in cultured cells. Our results suggest that specific affinity of the LC3 isoforms to the Atg13 LIR is required for proper autophagosome formation.

PMID:
24290141
DOI:
10.1016/j.str.2013.09.023
[Indexed for MEDLINE]
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