Insights into noncanonical E1 enzyme activation from the structure of autophagic E1 Atg7 with Atg8

Hong, Seung Beom; Kim, Byeong Won; Lee, Jun Young; Kim, Se Woong; Jeon, Hyesung; Kim, Joon; Song, Hyun Kyu

doi:10.1038/nsmb.2165

Cited by 93 publications

(108 citation statements)

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“…The putative CC region of NDP52 was based on the structure of the ROCK-I CC region (PDB accession code: 3O0Z) 43 and the structurally uncharacterized SKICH and UBZ domains were shown as ovals. The monomeric forms of LC3C and GAL8 were drawn with the Atg8 structure (PDB accession code: 3RUI) 44 and this study (PDB accession code: 4HAN), respectively. FP assay.…”

Section: Methodsmentioning

confidence: 99%

Structural basis for recognition of autophagic receptor NDP52 by the sugar receptor galectin-8

et al. 2013

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Infectious bacteria are cleared from mammalian cells by host autophagy in combination with other upstream cellular components, such as the autophagic receptor NDP52 and sugar receptor galectin-8. However, the detailed molecular basis of the interaction between these two receptors remains to be elucidated. Here, we report the biochemical characterization of both NDP52 and galectin-8 as well as the crystal structure of galectin-8 complexed with an NDP52 peptide. The unexpected observation of nicotinamide adenine dinucleotide located at the carbohydrate-binding site expands our knowledge of the sugar-binding specificity of galectin-8. The NDP52-galectin-8 complex structure explains the key determinants for recognition on both receptors and defines a special orientation of N-and C-terminal carbohydrate recognition domains of galectin-8. Dimeric NDP52 forms a ternary complex with two monomeric galectin-8 molecules as well as two LC3C molecules. These results lay the groundwork for understanding how host cells target bacterial pathogens for autophagy.

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Section: Methodsmentioning

confidence: 99%

Structural basis for recognition of autophagic receptor NDP52 by the sugar receptor galectin-8

et al. 2013

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“…The C-terminal tail of the ECTD shows no secondary structure and can interact with Atg8. Biochemical data further show that this interaction is important for recognition of Atg8 by Atg7 [158,159]. Based on the structural and biochemical data, Atg8 is first recognized by the ECTD C-terminal tail of Atg7.…”

Section: Two Ubl Protein Conjugation Systemsmentioning

confidence: 99%

“…It is unclear whether Atg3 will compete with Atg10 for interaction with Atg7. Previous studies show that Atg10 bound to Atg7 could be easily replaced by Atg3, but not the reverse, indicating that Atg3 has a higher affinity for binding Atg7 [159]. Atg10 possesses a conserved E2 core that is comprised of four β sheets and two α-helices.…”

Section: Two Ubl Protein Conjugation Systemsmentioning

confidence: 99%

The machinery of macroautophagy

et al. 2013

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Autophagy is a primarily degradative pathway that takes place in all eukaryotic cells. It is used for recycling cytoplasm to generate macromolecular building blocks and energy under stress conditions, to remove superfluous and damaged organelles to adapt to changing nutrient conditions and to maintain cellular homeostasis. In addition, autophagy plays a critical role in cytoprotection by preventing the accumulation of toxic proteins and through its action in various aspects of immunity including the elimination of invasive microbes and its participation in antigen presentation. The most prevalent form of autophagy is macroautophagy, and during this process, the cell forms a double-membrane sequestering compartment termed the phagophore, which matures into an autophagosome. Following delivery to the vacuole or lysosome, the cargo is degraded and the resulting macromolecules are released back into the cytosol for reuse. The past two decades have resulted in a tremendous increase with regard to the molecular studies of autophagy being carried out in yeast and other eukaryotes. Part of the surge in interest in this topic is due to the connection of autophagy with a wide range of human pathophysiologies including cancer, myopathies, diabetes and neurodegenerative disease. However, there are still many aspects of autophagy that remain unclear, including the process of phagophore formation, the regulatory mechanisms that control its induction and the function of most of the autophagy-related proteins. In this review, we focus on macroautophagy, briefly describing the discovery of this process in mammalian cells, discussing the current views concerning the donor membrane that forms the phagophore, and characterizing the autophagy machinery including the available structural information.

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“…This protein is also activated by Atg7, and structural studies have provided insight into the mechanism by which Atg7 can act as a common E1 for two different conjugating enzymes (Hong et al 2011;Noda et al 2011;Taherbhoy et al 2011;Yamaguchi et al 2012a). The activated Atg12 is then transferred to the Atg10-conjugating enzyme (Shintani et al 1999), which catalyzes the formation of a covalent bond between the Cterminal glycine of Atg12 and an internal lysine of Atg5 (Mizushima et al 1998), a protein that also contains two ubiquitin-like structural domains (Matsushita et al 2007).…”

Section: Macroautophagymentioning

confidence: 99%

Autophagic Processes in Yeast: Mechanism, Machinery and Regulation

2013

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Autophagy refers to a group of processes that involve degradation of cytoplasmic components including cytosol, macromolecular complexes, and organelles, within the vacuole or the lysosome of higher eukaryotes. The various types of autophagy have attracted increasing attention for at least two reasons. First, autophagy provides a compelling example of dynamic rearrangements of subcellular membranes involving issues of protein trafficking and organelle identity, and thus it is fascinating for researchers interested in questions pertinent to basic cell biology. Second, autophagy plays a central role in normal development and cell homeostasis, and, as a result, autophagic dysfunctions are associated with a range of illnesses including cancer, diabetes, myopathies, some types of neurodegeneration, and liver and heart diseases. That said, this review focuses on autophagy in yeast. Many aspects of autophagy are conserved from yeast to human; in particular, this applies to the gene products mediating these pathways as well as some of the signaling cascades regulating it, so that the information we relate is relevant to higher eukaryotes. Indeed, as with many cellular pathways, the initial molecular insights were made possible due to genetic studies in Saccharomyces cerevisiae and other fungi. TABLE OF CONTENTS Abstract 341Introduction 342

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Insights into noncanonical E1 enzyme activation from the structure of autophagic E1 Atg7 with Atg8

Cited by 93 publications

References 50 publications

Structural basis for recognition of autophagic receptor NDP52 by the sugar receptor galectin-8

Structural basis for recognition of autophagic receptor NDP52 by the sugar receptor galectin-8

The machinery of macroautophagy

Autophagic Processes in Yeast: Mechanism, Machinery and Regulation

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