Architecture and dynamics of the autophagic phosphatidylinositol 3-kinase complex.

Article Details

Citation

Baskaran S, Carlson LA, Stjepanovic G, Young LN, Kim do J, Grob P, Stanley RE, Nogales E, Hurley JH

Architecture and dynamics of the autophagic phosphatidylinositol 3-kinase complex.

Elife. 2014 Dec 9;3. doi: 10.7554/eLife.05115.

PubMed ID
25490155 [ View in PubMed
]
Abstract

The class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1) that functions in early autophagy consists of the lipid kinase VPS34, the scaffolding protein VPS15, the tumor suppressor BECN1, and the autophagy-specific subunit ATG14. The structure of the ATG14-containing PI3KC3-C1 was determined by single-particle EM, revealing a V-shaped architecture. All of the ordered domains of VPS34, VPS15, and BECN1 were mapped by MBP tagging. The dynamics of the complex were defined using hydrogen-deuterium exchange, revealing a novel 20-residue ordered region C-terminal to the VPS34 C2 domain. VPS15 organizes the complex and serves as a bridge between VPS34 and the ATG14:BECN1 subcomplex. Dynamic transitions occur in which the lipid kinase domain is ejected from the complex and VPS15 pivots at the base of the V. The N-terminus of BECN1, the target for signaling inputs, resides near the pivot point. These observations provide a framework for understanding the allosteric regulation of lipid kinase activity.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Phosphatidylinositol 3-kinase catalytic subunit type 3Q8NEB9Details
Beclin-1Q14457Details