【摘 要】
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The class Ⅲ phosphatidylinositol 3-kinase complex Ⅰ (PI3KC3-C1) that functions in early autophagy consists of the lipid kinase VPS34, the scaffolding prot
【机 构】
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Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United State
【出 处】
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The 7th International Symposium on Autophagy 2015(第七届自噬国际研讨会
论文部分内容阅读
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.
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