Cited by 89Autophagy in Disease and TherapyCellular transport and secretionPI3K/AKT/mTOR signaling in cancer

Dynamics and architecture of the NRBF2-containing phosphatidylinositol 3-kinase complex I of autophagy

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Young, Lindsey N., Cho, Kelvin, Lawrence, Rosalie, Zoncu, Roberto, Hurley, James H.·2016·Proceedings of the National Academy of Sciences

Abstract

Significance: Autophagy (self-eating) is an essential process for cellular self-renewal. It is initiated by the ULK1 (unc-51 like autophagy activating kinase 1) protein kinase complex and the class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1) lipid kinase complex, and understanding the structures of these large complexes is central to understanding how autophagy is initiated. Here we show that the protein nuclear receptor binding factor 2 (NRBF2) is the fifth subunit of the active form of PI3KC3-C1 and the NRBF2-containing complex is 10-fold more active. NRBF2 binds at the base of the V-shaped PI3KC3 architecture and changes protein motions, which may explain the change in enzyme activity. NRBF2 converts PI3KC3-C1 into a dimer, which changes how we think about the role of PI3KC3 in vesicle tethering.

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  1. Lander GC, et al. (2009) Image Processing. Access 166(1):95-102.

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Authors
Young, L. N., Cho, K., Lawrence, R., Zoncu, R., & Hurley, J. H.
Affiliations
QB3 (US)
Corresponding author
Hurley, James H.
Venue
Proceedings of the National Academy of Sciences
Published
2016-07-06
Volume
113
Issue
29
Pages
8224-8229
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2469694753
Cited by
89
References
38
Citations by year
2026: 6 · 2025: 8 · 2024: 6 · 2023: 5 · 2022: 5 · 2021: 21 · 2020: 10 · 2019: 8 · 2018: 11 · 2017: 6 · 2016: 3
FWCI
8.75
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
HHS | NIH | National Institute of General Medical Sciences (R01GM111730)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords
class III phosphatidylinositol 3-kinase, autophagy initiation, Vps34, VPS15, Beclin-1, ATG14, complex architecture, lipid kinase activity, homodimerization, protein-protein interaction
MeSH terms
Autophagy-Related Proteins, Beclin-1, Autophagy, Escherichia coli, Humans, Trans-Activators, Adaptor Proteins, Vesicular Transport, HEK293 Cells, Class III Phosphatidylinositol 3-Kinases

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