8kbx | pdb_00008kbx

Cryo-EM structure of human ATG2A-WIPI4 complex

Structural highlights

8kbx is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.23Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

WIPI4_HUMAN Infantile spasms syndrome;Beta-propeller protein-associated neurodegeneration. The disease is caused by variants affecting the gene represented in this entry.

Function

WIPI4_HUMAN Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation (PubMed:23435086, PubMed:28561066). Binds phosphatidylinositol 3-phosphate (PtdIns3P) (PubMed:28561066). Activated by the STK11/AMPK signaling pathway upon starvation, WDR45 is involved in autophagosome assembly downstream of WIPI2, regulating the size of forming autophagosomes (PubMed:28561066). Together with WIPI1, promotes ATG2 (ATG2A or ATG2B)-mediated lipid transfer by enhancing ATG2-association with phosphatidylinositol 3-monophosphate (PI3P)-containing membranes (PubMed:31271352). Probably recruited to membranes through its PtdIns3P activity (PubMed:28561066).^[1] ^[2] ^[3]

References

↑ Saitsu H, Nishimura T, Muramatsu K, Kodera H, Kumada S, Sugai K, Kasai-Yoshida E, Sawaura N, Nishida H, Hoshino A, Ryujin F, Yoshioka S, Nishiyama K, Kondo Y, Tsurusaki Y, Nakashima M, Miyake N, Arakawa H, Kato M, Mizushima N, Matsumoto N. De novo mutations in the autophagy gene WDR45 cause static encephalopathy of childhood with neurodegeneration in adulthood. Nat Genet. 2013 Apr;45(4):445-9, 449e1. PMID:23435086 doi:10.1038/ng.2562
↑ Bakula D, Muller AJ, Zuleger T, Takacs Z, Franz-Wachtel M, Thost AK, Brigger D, Tschan MP, Frickey T, Robenek H, Macek B, Proikas-Cezanne T. WIPI3 and WIPI4 beta-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy. Nat Commun. 2017 May 31;8:15637. doi: 10.1038/ncomms15637. PMID:28561066 doi:https://dx.doi.org/10.1038/ncomms15637
↑ Maeda S, Otomo C, Otomo T. The autophagic membrane tether ATG2A transfers lipids between membranes. Elife. 2019 Jul 4;8:e45777. PMID:31271352 doi:10.7554/eLife.45777

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OCA

[1] Saitsu H, Nishimura T, Muramatsu K, Kodera H, Kumada S, Sugai K, Kasai-Yoshida E, Sawaura N, Nishida H, Hoshino A, Ryujin F, Yoshioka S, Nishiyama K, Kondo Y, Tsurusaki Y, Nakashima M, Miyake N, Arakawa H, Kato M, Mizushima N, Matsumoto N. De novo mutations in the autophagy gene WDR45 cause static encephalopathy of childhood with neurodegeneration in adulthood. Nat Genet. 2013 Apr;45(4):445-9, 449e1. PMID:23435086 doi:10.1038/ng.2562

[2] Bakula D, Muller AJ, Zuleger T, Takacs Z, Franz-Wachtel M, Thost AK, Brigger D, Tschan MP, Frickey T, Robenek H, Macek B, Proikas-Cezanne T. WIPI3 and WIPI4 beta-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy. Nat Commun. 2017 May 31;8:15637. doi: 10.1038/ncomms15637. PMID:28561066 doi:https://dx.doi.org/10.1038/ncomms15637

[3] Maeda S, Otomo C, Otomo T. The autophagic membrane tether ATG2A transfers lipids between membranes. Elife. 2019 Jul 4;8:e45777. PMID:31271352 doi:10.7554/eLife.45777

[1]

[2]

[3]

8kbx | pdb_00008kbx

Cryo-EM structure of human ATG2A-WIPI4 complex

Structural highlights

Disease

Function

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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