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Noda N.N.,Institute of Microbial Chemistry BIKAKEN | Noda N.N.,Japan Science and Technology Agency | Inagaki F.,Japan Science and Technology Agency | Inagaki F.,Hokkaido University
Annual Review of Biophysics | Year: 2015

The formation of the autophagosome, a landmark event in autophagy, is accomplished by the concerted actions of Atg proteins. The initial step of starvation-induced autophagy in yeast is the assembly of the Atg1 complex, which, with the help of other Atg groups, recruits Atg conjugation systems and initiates the formation of the autophagosome. In this review, we describe from a structural-biological point of view the structure, interaction, and molecular roles of Atg proteins, especially those in the Atg1 complex and in the Atg conjugation systems. © Copyright ©2015 by Annual Reviews. All rights reserved. Source


Noda N.N.,Institute of Microbial Chemistry BIKAKEN | Noda N.N.,Japan Science and Technology Agency | Fujioka Y.,Institute of Microbial Chemistry BIKAKEN
Cellular and Molecular Life Sciences | Year: 2015

Autophagosome formation, a landmark event in autophagy, is accomplished by the concerted actions of Atg proteins. Among all Atg proteins, Atg1 kinase in yeast and its counterpart in higher eukaryotes, ULK1 kinase, function as the most upstream factor in this process and mediate autophagy initiation. In this review, we summarize current knowledge of the structure, molecular function, and regulation of Atg1 family kinases in the initiation of autophagy. © 2015 The Author(s). Source


Suzuki H.,Institute of Microbial Chemistry BIKAKEN | Kaizuka T.,University of Tokyo | Mizushima N.,University of Tokyo | Noda N.N.,Institute of Microbial Chemistry BIKAKEN | Noda N.N.,Japan Science and Technology Agency
Nature Structural and Molecular Biology | Year: 2015

Atg101 is an essential component of the autophagy-initiating ULK complex in higher eukaryotes, but it is absent from the functionally equivalent Atg1 complex in budding yeast. Here, we report the crystal structure of the fission yeast Atg101-Atg13 complex. Atg101 has a Hop1, Rev7 and Mad2 (HORMA) architecture similar to that of Atg13. Mad2 HORMA has two distinct conformations (O-Mad2 and C-Mad2), and, intriguingly, Atg101 resembles O-Mad2 rather than the C-Mad2-like Atg13. Atg13 HORMA from higher eukaryotes possesses an inherently unstable fold, which is stabilized by Atg101 via interactions analogous to those between O-Mad2 and C-Mad2. Mutational studies revealed that Atg101 is responsible for recruiting downstream factors to the autophagosome-formation site in mammals via a newly identified WF finger. These data define the molecular functions of Atg101, providing a basis for elucidating the molecular mechanisms of mammalian autophagy initiation by the ULK complex. © 2015 Nature America, Inc. All rights reserved. Source


Yin L.,Institute of Microbial Chemistry BIKAKEN | Bao Y.,Institute of Microbial Chemistry BIKAKEN | Kumagai N.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Japan Science and Technology Agency
Journal of the American Chemical Society | Year: 2013

Catalytic asymmetric hydrophosphonylation of aromatic and aliphatic N-thiophosphinoyl ketimines with dialkyl phosphite was efficiently promoted by as little as 0.5 mol% of catalyst loading at ambient temperature. The catalyst can be recovered for repeated use, and facile removal of the thiophosphinoyl group allowed for ready access to the phosphonic acid analogue of enantioenriched α,α-disubstituted α-amino acids. © 2013 American Chemical Society. Source


Yin L.,Institute of Microbial Chemistry BIKAKEN | Takada H.,Institute of Microbial Chemistry BIKAKEN | Lin S.,Institute of Microbial Chemistry BIKAKEN | Kumagai N.,Institute of Microbial Chemistry BIKAKEN | And 2 more authors.
Angewandte Chemie - International Edition | Year: 2014

Soft Lewis acid/Brønsted base cooperative catalysts have enabled direct catalytic asymmetric vinylogous conjugate addition of α,β- and β,γ-unsaturated butyrolactones to α,β-unsaturated thioamides with perfect atom economy. When using α-angelica lactone and its derivatives as pronucleophiles, as little as 0.5 mol % catalyst loading was sufficient to complete the reaction necessary to construct consecutive tri- and tetrasubstituted stereogenic centers in a highly diastereo- and enantioselective fashion. Soft spot: Soft Lewis acid/Brønsted base cooperative catalysts have enabled the title reaction of α,β- and β,γ- unsaturated butyrolactones with perfect atom economy. When using α-angelica lactone and its derivatives as pronucleophiles, a 0.5 mol % catalyst loading was sufficient to complete the reaction to construct consecutive tri- and tetrasubstituted stereogenic centers in a highly diastereo- and enantioselective fashion. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

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