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ATG12

The Experts below are selected from a list of 3810 Experts worldwide ranked by ideXlab platform

Fuyuhiko Inagaki – 1st expert on this subject based on the ideXlab platform

  • Architecture of the ATG12–Atg5–Atg16 Complex and its Molecular Role in Autophagy
    Autophagy: Cancer Other Pathologies Inflammation Immunity Infection and Aging, 2020
    Co-Authors: Nobuo N Noda, Fuyuhiko Inagaki

    Abstract:

    Atg5 is covalently modified with ATG12 via reactions that are similar to ubiquitination, and it noncovalently interacts with Atg16. Formation of the ATG12–Atg5–Atg16 complex is essential for its E3-like function: facilitation of Atg8 transfer from Atg3 to phosphatidylethanolamine at autophagic membranes. Structural studies on the ATG12–Atg5–Atg16 complex revealed that the unique architecture of this protein complex is totally distinct from the other E3 enzymes. The ATG12–Atg5–Atg16 complex interacts directly with Atg3 via ATG12, and enhances the conjugase activity of Atg3 by rearranging its catalytic center, while it is targeted to the membranes via Atg5 and Atg16, and promotes the transfer of Atg8 from Atg3 to the membranes.

  • architecture of the ATG12 atg5 atg16 complex and its molecular role in autophagy
    Autophagy: Cancer Other Pathologies Inflammation Immunity Infection and Aging#R##N#Volume 3 – Mitophagy, 2014
    Co-Authors: Nobuo N Noda, Fuyuhiko Inagaki

    Abstract:

    Atg5 is covalently modified with ATG12 via reactions that are similar to ubiquitination, and it noncovalently interacts with Atg16. Formation of the ATG12–Atg5–Atg16 complex is essential for its E3-like function: facilitation of Atg8 transfer from Atg3 to phosphatidylethanolamine at autophagic membranes. Structural studies on the ATG12–Atg5–Atg16 complex revealed that the unique architecture of this protein complex is totally distinct from the other E3 enzymes. The ATG12–Atg5–Atg16 complex interacts directly with Atg3 via ATG12, and enhances the conjugase activity of Atg3 by rearranging its catalytic center, while it is targeted to the membranes via Atg5 and Atg16, and promotes the transfer of Atg8 from Atg3 to the membranes.

  • ATG12 atg5 conjugate enhances e2 activity of atg3 by rearranging its catalytic site
    Nature Structural & Molecular Biology, 2013
    Co-Authors: Machiko Sakohnakatogawa, Hitoshi Nakatogawa, Hiromi Kirisako, Eri Asai, Nobuo N Noda, Fuyuhiko Inagaki, Kazuaki Matoba, Junko Ishii, Yoshinori Ohsumi

    Abstract:

    In the yeast autophagy system, the ATG12–Atg5 conjugate acts as an E3 to promote the E2 activity of Atg3, which conjugates Atg8 to phosphatidylethanolamine. Now structural and biochemical analyses reveal that ATG12–Atg5 induces a rearrangement in the catalytic center of Atg3, which employs a threonine residue in addition to the active cysteine to catalyze the conjugation reaction.

Yoshinori Ohsumi – 2nd expert on this subject based on the ideXlab platform

  • Two distinct mechanisms target the autophagy-related E3 complex to the pre-autophagosomal structure.
    eLife, 2019
    Co-Authors: Kumi Harada, Yoshinori Ohsumi, Hiromi Kirisako, Machiko Sakoh-nakatogawa, Hayashi Yamamoto, Yayoi Kimura, Hisashi Hirano, Tetsuya Kotani, Yu Oikawa, Hitoshi Nakatogawa

    Abstract:

    In autophagy, Atg proteins organize the pre-autophagosomal structure (PAS) to initiate autophagosome formation. Previous studies in yeast revealed that the autophagy-related E3 complex ATG12-Atg5-Atg16 is recruited to the PAS via Atg16 interaction with Atg21, which binds phosphatidylinositol 3-phosphate (PI3P) produced at the PAS, to stimulate conjugation of the ubiquitin-like protein Atg8 to phosphatidylethanolamine. Here, we discover a novel mechanism for the PAS targeting of ATG12-Atg5-Atg16, which is mediated by the interaction of ATG12 with the Atg1 kinase complex that serves as a scaffold for PAS organization. While autophagy is partially defective without one of these mechanisms, cells lacking both completely lose the PAS localization of ATG12-Atg5-Atg16 and show no autophagic activity. As with the PI3P-dependent mechanism, ATG12-Atg5-Atg16 recruited via the ATG12-dependent mechanism stimulates Atg8 lipidation, but also has the specific function of facilitating PAS scaffold assembly. Thus, this study significantly advances our understanding of the nucleation step in autophagosome formation.

  • membrane morphology is actively transformed by covalent binding of the protein atg8 to pe lipids
    PLOS ONE, 2014
    Co-Authors: Roland L Knorr, Yoshinori Ohsumi, Hitoshi Nakatogawa, Reinhard Lipowsky, Tobias Baumgart, Rumiana Dimova

    Abstract:

    Autophagy is a cellular degradation pathway involving the shape transformation of lipid bilayers. During the onset of autophagy, the water-soluble protein Atg8 binds covalently to phosphatdylethanolamines (PEs) in the membrane in an ubiquitin-like reaction coupled to ATP hydrolysis. We reconstituted the Atg8 conjugation system in giant and nm-sized vesicles with a minimal set of enzymes and observed that formation of Atg8-PE on giant vesicles can cause substantial tubulation of membranes even in the absence of ATG12-Atg5-Atg16. Our findings show that ubiquitin-like processes can actively change properties of lipid membranes and that membrane crowding by proteins can be dynamically regulated in cells. Furthermore we provide evidence for curvature sorting of Atg8-PE. Curvature generation and sorting are directly linked to organelle shapes and, thus, to biological function. Our results suggest that a positive feedback exists between the ubiquitin-like reaction and the membrane curvature, which is important for dynamic shape changes of cell membranes, such as those involved in the formation of autophagosomes.

  • hrr25 triggers selective autophagy related pathways by phosphorylating receptor proteins
    Journal of Cell Biology, 2014
    Co-Authors: Chikara Tanaka, Yoshinori Ohsumi, Keisuke Mochida, Hiromi Kirisako, Michiko Koizumi, Eri Asai, Machiko Sakohnakatogawa, Hitoshi Nakatogawa

    Abstract:

    In selective autophagy, degradation targets are specifically recognized, sequestered by the autophagosome, and transported into the lysosome or vacuole. Previous studies delineated the molecular basis by which the autophagy machinery recognizes those targets, but the regulation of this process is still poorly understood. In this paper, we find that the highly conserved multifunctional kinase Hrr25 regulates two distinct selective autophagy–related pathways in Saccharomyces cerevisiae. Hrr25 is responsible for the phosphorylation of two receptor proteins: Atg19, which recognizes the assembly of vacuolar enzymes in the cytoplasm-to-vacuole targeting pathway, and Atg36, which recognizes superfluous peroxisomes in pexophagy. Hrr25-mediated phosphorylation enhances the interactions of these receptors with the common adaptor Atg11, which recruits the core autophagy-related proteins that mediate the formation of the autophagosomal membrane. Thus, this study introduces regulation of selective autophagy as a new role of Hrr25 and, together with other recent studies, reveals that different selective autophagy–related pathways are regulated by a uniform mechanism: phosphoregulation of the receptor–adaptor interaction.

Nobuo N Noda – 3rd expert on this subject based on the ideXlab platform

  • Architecture of the ATG12–Atg5–Atg16 Complex and its Molecular Role in Autophagy
    Autophagy: Cancer Other Pathologies Inflammation Immunity Infection and Aging, 2020
    Co-Authors: Nobuo N Noda, Fuyuhiko Inagaki

    Abstract:

    Atg5 is covalently modified with ATG12 via reactions that are similar to ubiquitination, and it noncovalently interacts with Atg16. Formation of the ATG12–Atg5–Atg16 complex is essential for its E3-like function: facilitation of Atg8 transfer from Atg3 to phosphatidylethanolamine at autophagic membranes. Structural studies on the ATG12–Atg5–Atg16 complex revealed that the unique architecture of this protein complex is totally distinct from the other E3 enzymes. The ATG12–Atg5–Atg16 complex interacts directly with Atg3 via ATG12, and enhances the conjugase activity of Atg3 by rearranging its catalytic center, while it is targeted to the membranes via Atg5 and Atg16, and promotes the transfer of Atg8 from Atg3 to the membranes.

  • Evolution from covalent conjugation to non-covalent interaction in the ubiquitin-like ATG12 system
    Nature Structural & Molecular Biology, 2019
    Co-Authors: Yu Pang, Hayashi Yamamoto, Nobuo N Noda, Hirokazu Sakamoto, Joe Kimanthi Mutungi, Mayurbhai Himatbhai Sahani, Yoshitaka Kurikawa, Kiyoshi Kita, Yasuyoshi Sakai

    Abstract:

    Ubiquitin or ubiquitin-like proteins can be covalently conjugated to multiple proteins that do not necessarily have binding interfaces. Here, we show that an evolutionary transition from covalent conjugation to non-covalent interaction has occurred in the ubiquitin-like autophagy-related 12 (ATG12) conjugation system. ATG12 is covalently conjugated to its sole substrate, ATG5, by a ubiquitylation-like mechanism. However, the apicomplexan parasites Plasmodium and Toxoplasma and some yeast species such as Komagataella phaffii (previously Pichia pastoris) lack the E2-like enzyme ATG10 and the most carboxy (C)-terminal glycine of ATG12, both of which are required for covalent linkage. Instead, ATG12 in these organisms forms a non-covalent complex with ATG5. This non-covalent ATG12–ATG5 complex retains the ability to facilitate ATG8–phosphatidylethanolamine conjugation. These results suggest that ubiquitin-like covalent conjugation can evolve to a simpler non-covalent interaction, most probably when the system has a limited number of targets.

  • the intrinsically disordered protein atg13 mediates supramolecular assembly of autophagy initiation complexes
    Developmental Cell, 2016
    Co-Authors: Hayashi Yamamoto, Yuko Fujioka, Sho Suzuki, Daisuke Noshiro, Hironori Suzuki, Chika Kondokakuta, Yayoi Kimura, Hisashi Hirano, Toshio Ando, Nobuo N Noda

    Abstract:

    Autophagosome formation in yeast entails starvation-induced assembly of the pre-autophagosomal structure (PAS), in which multiple Atg1 complexes (composed of Atg1, Atg13, and the Atg17-Atg29-Atg31 subcomplex) are initially engaged. However, the molecular mechanisms underlying the multimeric assembly of these complexes remain unclear. Using structural and biological techniques, we herein demonstrate that Atg13 has a large intrinsically disordered region (IDR) and interacts with two distinct Atg17 molecules using two binding regions in the IDR. We further reveal that these two binding regions are essential not only for Atg1 complex assembly in vitro, but also for PAS organization in vivo. These findings underscore the structural and functional significance of the IDR of Atg13 in autophagy initiation: Atg13 provides intercomplex linkages between Atg17-Atg29-Atg31 complexes, thereby leading to supramolecular self-assembly of Atg1 complexes, in turn accelerating the initial events of autophagy, including autophosphorylation of Atg1, recruitment of Atg9 vesicles, and phosphorylation of Atg9 by Atg1.