Systematic analysis of ATG13 domain requirements for autophagy induction

Wallot-Hieke, Nora; Verma, Neha; Schlütermann, David; Berleth, Niklas; Deitersen, Jana; Böhler, Philip; Stuhldreier, Fabian; Wu, Wenxian; Seggewiß, Sabine; Peter, Christoph; Gohlke, Holger; Mizushima, Noboru; Stork, Björn

doi:10.1080/15548627.2017.1387342

Cited by 47 publications

(60 citation statements)

References 74 publications

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“…These data suggest that the ATG13 MR, not the HORMA dimer is the FIP200 NTD binding site. This is consistent with the finding that deletion of ATG13 isoform2 348-373 blocks FIP200 interaction (Wallot-Hieke et al, 2018). This is also consistent with the NSEM result that in the FIP200 NTD-ATG13-ATG101, the HORMA domain dimer density was averaged out in 2D classifications (Fig.…”

Section: Mapping the Fip200 Binding Site On Atg13supporting

confidence: 92%

“…S2B). Taken together, these experiments show the FIP200-ATG13 and ULK1-ATG13 interactions are individually nonessential for mitophagy, similar to the findings for starvation-induced autophagy in MEFs (Wallot-Hieke et al, 2018).…”

Section: Mapping the Fip200 Binding Site On Atg13supporting

confidence: 76%

“…It was previously found that in atg13 KO MEFs rescued by ATG13 construct expression, loss of the N-terminal part of the ATG13 MR has no effect on starvation-induced autophagy and only a slight effect on torin-induced autophagy (Wallot- Hieke et al, 2018). We assessed mitophagy in HeLa cells using a mito-mKeima assay (Vargas et al, 2019).…”

Section: Mapping the Fip200 Binding Site On Atg13mentioning

confidence: 99%

“…S2B). A mutant ATG13 lacking the C-terminal ULK1/2 binding site residues (ATG13-ΔC) was also examined (Wallot- Hieke et al, 2018).…”

Section: Mapping the Fip200 Binding Site On Atg13mentioning

confidence: 99%

“…ULK1 contains a C-terminal early autophagy targeting/tethering (EAT) domain, which is connected to the kinase domain by a ~550 residue long intrinsically disordered region (IDR) and targets ULK1 by binding to a motif in the C-terminus of ATG13 (Chan et al, 2009;Hieke et al, 2015). ATG13 consists of an N-terminal HORMA (Hop/Rev7/Mad2) domain, which dimerizes with the HORMA domain of ATG101 (Qi et al, 2015;Suzuki et al, 2015) and a long C-terminal IDR which binds to FIP200 (Jung et al, 2009;Wallot-Hieke et al, 2018) and ULK1 (Hieke et al, 2015;Wallot-Hieke et al, 2018). The ATG101 HORMA contains an exposed WF finger motif that is important for autophagy (Suzuki et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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ULK complex organization in autophagy by a C-shaped FIP200 N-terminal domain dimer

Shi

Yokom

Wang

et al. 2019

Preprint

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The human ULK complex consists of ULK1/2, FIP200, ATG13, and ATG101. We found that the FIP200 N-terminal domain is a C-shaped dimer that binds directly to a single ATG13 molecule and serves as the organizing hub of the complex. AbstractThe autophagy-initiating human ULK complex consists of the kinase ULK1/2, FIP200, ATG13, and ATG101. Hydrogen-deuterium exchange mass spectrometry was used to map their mutual interactions. The N-terminal 640 residues (NTD) of FIP200 interact with the C-terminal IDR of ATG13. Mutations in these regions abolish their interaction. Negative stain electron microscopy (EM) and multiangle light scattering showed that FIP200 is a dimer whilst a single molecule each of the other subunits is present. The FIP200 NTD is flexible in the absence of ATG13, but in its presence adopts the shape of the letter C ~20 nm across. The ULK1 EAT domain interacts loosely with the NTD dimer, while the ATG13-ATG101 HORMA dimer does not contact the NTD. Cryo-EM of the NTD dimer revealed a structure similarity to the scaffold domain of TBK1, suggesting an evolutionary similarity between the autophagy initiating TBK1 kinase and the ULK1 kinase complex.

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Section: Mapping the Fip200 Binding Site On Atg13supporting

confidence: 92%

Section: Mapping the Fip200 Binding Site On Atg13supporting

confidence: 76%

Section: Mapping the Fip200 Binding Site On Atg13mentioning

confidence: 99%

“…S2B). A mutant ATG13 lacking the C-terminal ULK1/2 binding site residues (ATG13-ΔC) was also examined (Wallot- Hieke et al, 2018).…”

Section: Mapping the Fip200 Binding Site On Atg13mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

ULK complex organization in autophagy by a C-shaped FIP200 N-terminal domain dimer

Shi

Yokom

Wang

et al. 2019

Preprint

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The role of the HORMA domain proteins ATG13 and ATG101 in initiating autophagosome biogenesis

Nguyen,

Faesen

2023

FEBS Letters

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Autophagy is a process of regulated degradation. It eliminates damaged and unnecessary cellular components by engulfing them with a de novo‐generated organelle: the double‐membrane autophagosome. The last three decades have provided us with a detailed parts list of the autophagy initiation machinery, have developed important insights into how these processes function and have identified regulatory proteins. It is now clear that autophagosome biogenesis requires the timely assembly of a complex machinery. However, it is unclear how a putative stable machine is assembled and disassembled, and how the different parts cooperate to perform its overall function. Although they have long been somewhat enigmatic in their precise role, HORMA domain proteins (first identified in Hop1p, Rev7p and MAD2 proteins) autophagy‐related protein 13 (ATG13) and ATG101 of the ULK‐kinase complex have emerged as important coordinators of the autophagy‐initiating subcomplexes. Here, we will particularly focus on ATG13 and ATG101 and the role of their unusual metamorphosis in initiating autophagosome biogenesis. We will also explore how this metamorphosis could potentially be purposefully rate‐limiting and speculate on how it could regulate the spontaneous self‐assembly of the autophagy‐initiating machinery.

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Autophagy in health and disease: From molecular mechanisms to therapeutic target

Wang

Shi

et al. 2022

MedComm

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Macroautophagy/autophagy is an evolutionally conserved catabolic process in which cytosolic contents, such as aggregated proteins, dysfunctional organelle, or invading pathogens, are sequestered by the double‐membrane structure termed autophagosome and delivered to lysosome for degradation. Over the past two decades, autophagy has been extensively studied, from the molecular mechanisms, biological functions, implications in various human diseases, to development of autophagy‐related therapeutics. This review will focus on the latest development of autophagy research, covering molecular mechanisms in control of autophagosome biogenesis and autophagosome–lysosome fusion, and the upstream regulatory pathways including the AMPK and MTORC1 pathways. We will also provide a systematic discussion on the implication of autophagy in various human diseases, including cancer, neurodegenerative disorders (Alzheimer disease, Parkinson disease, Huntington's disease, and Amyotrophic lateral sclerosis), metabolic diseases (obesity and diabetes), viral infection especially SARS‐Cov‐2 and COVID‐19, cardiovascular diseases (cardiac ischemia/reperfusion and cardiomyopathy), and aging. Finally, we will also summarize the development of pharmacological agents that have therapeutic potential for clinical applications via targeting the autophagy pathway. It is believed that decades of hard work on autophagy research is eventually to bring real and tangible benefits for improvement of human health and control of human diseases.

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Systematic analysis of ATG13 domain requirements for autophagy induction

Cited by 47 publications

References 74 publications

ULK complex organization in autophagy by a C-shaped FIP200 N-terminal domain dimer

ULK complex organization in autophagy by a C-shaped FIP200 N-terminal domain dimer

The role of the HORMA domain proteins ATG13 and ATG101 in initiating autophagosome biogenesis

Autophagy in health and disease: From molecular mechanisms to therapeutic target

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