Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural pathway for PI3-kinase regulation by VPS15 in autophagy.
Journal, issue, pages	Science, Vol. 388, Issue 6743, Page eadl3787, Year 2025
Publish date	Apr 11, 2025
Authors	Annan S I Cook / Minghao Chen / Thanh N Nguyen / Ainara Claveras Cabezudo / Grace Khuu / Shanlin Rao / Samantha N Garcia / Mingxuan Yang / Anthony T Iavarone / Xuefeng Ren / Michael Lazarou / Gerhard Hummer / James H Hurley /
PubMed Abstract	The class III phosphatidylinositol-3 kinase complexes I and II (PI3KC3-C1 and PI3KC3-C2) have vital roles in macroautophagy and endosomal maturation, respectively. We elucidated a structural pathway ...The class III phosphatidylinositol-3 kinase complexes I and II (PI3KC3-C1 and PI3KC3-C2) have vital roles in macroautophagy and endosomal maturation, respectively. We elucidated a structural pathway of enzyme activation through cryo-electron microscopy analysis of PI3KC3-C1. The inactive conformation of the VPS15 pseudokinase stabilizes the inactive conformation, sequestering its -myristate in the N-lobe of the pseudokinase. Upon activation, the myristate is liberated such that the VPS34 lipid kinase catalyzes phosphatidylinositol-3 phosphate production on membranes. The VPS15 pseudokinase domain binds tightly to guanosine triphosphate and stabilizes a web of interactions to autoinhibit the cytosolic complex and promote activation upon membrane binding. These findings show in atomistic detail how the VPS34 lipid kinase is activated in the context of a complete PI3K complex.
External links	Science / PubMed:39913640 / PubMed Central
Methods	EM (single particle)
Resolution	2.62 - 5.0 Å
Structure data	EMDB-48230: PI3KC3-C1 bound to RAB1A, no VPS34 Kinase domain Method: EM (single particle) / Resolution: 2.73 Å EMDB-48231: Local Refinement of VPS15 pseudokinase domain and helical repeats Method: EM (single particle) / Resolution: 2.67 Å EMDB-48232: PI3KC3-C1 Bound to RAB1A local refinement of RAB1A/VPS34 interface Method: EM (single particle) / Resolution: 2.68 Å EMDB-48233: PI3KC3-C1 bound to RAB1A. Local refinement of Bara like domains of BECN1 and ATG14, and VPS15 WD40 domain Method: EM (single particle) / Resolution: 2.62 Å EMDB-48257: PI3KC3-C1 bound to RAB1A in the inactive state. Consensus refinement Method: EM (single particle) / Resolution: 3.1 Å EMDB-48258: PI3KC3C1 bound to RAB1A, Inactive state, VPS34 kinase domain local refinement Method: EM (single particle) / Resolution: 3.1 Å EMDB-48259: PI3KC3-C1 bound to RAB1A. Consensus inactive state refinement of particle subset with strongest kinase domain density Method: EM (single particle) / Resolution: 3.3 Å EMDB-48260: PI3KC3-C1 bound to RAB1A. Local refinement of VPS34KD in the inactive state, particle subset Method: EM (single particle) / Resolution: 3.3 Å EMDB-48272: PI3KC3-C1 bound to RAB1A. VPS34 kinase domain in the active conformation, consensus reconstruction Method: EM (single particle) / Resolution: 5.0 Å 48276 9mhf EMDB-48276, PDB-9mhf: Cryo-EM reconstruction of PI3KC3-C1 in complex with Human RAB1A(Q70L) Method: EM (single particle) / Resolution: 2.73 Å 48277 9mhg EMDB-48277, PDB-9mhg: Cryo EM reconstruction of PI3KC3-C1 in complex with Human RAB1A(Q70L), VPS34 kinase domain in the inactive conformation Method: EM (single particle) / Resolution: 3.2 Å 48278 9mhh EMDB-48278, PDB-9mhh: PI3KC3-C1 in complex with RAB1A. VPS34 kinase domain active conformation Method: EM (single particle) / Resolution: 4.5 Å
Chemicals	ChemComp-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying moleculeYM ChemComp-MG: Unknown entry ChemComp-MYR: MYRISTIC ACID ChemComp-HOH*: WATER
Source	homo sapiens (human)
Keywords	SIGNALING PROTEIN / Complex / GTPase / GTP-binding / Autophagy / Kinase / Lipid Kinase