J. E. Burke

Structure of Calcineurin bound to PI4KA reveals dual interface in both PI4KA and FAM126A

The paper reports a cryo-EM structure of Calcineurin bound to PI4KA, revealing direct interactions with both PI4KA and FAM126A and their conserved binding sequences.

Spartin-mediated lipid transfer facilitates lipid droplet turnover

This study identifies spartin as a lipid transfer protein essential for lipid droplet turnover via lipophagy, revealing a new lipid transport module in its senescence domain.

ESAT-6 undergoes self-association at phagosomal pH and an ESAT-6 specific nanobody restricts M. tuberculosis growth in macrophages

This study investigates ESAT-6's self-association under acidic conditions and shows an ESAT-6-specific nanobody inhibits M. tuberculosis growth in macrophages.

Allosteric activation or inhibition of PI3Kγ mediated through conformational changes in the p110γ helical domain

This study identifies the helical domain of p110γ as an allosteric regulator of PI3Kγ activity, showing distinct roles in p110γ-p84 and p110γ-p101 complexes through phosphorylation or nanobody binding.

Structural insights into perilipin 3 membrane association in response to diacylglycerol accumulation

The paper investigates how lipid composition, specifically phosphatidic acid and diacylglycerol, affects PLIN3 recruitment to membranes and LDs, revealing structural changes in the PAT domain.

Molecular basis for differential activation of p101 and p84 complexes of PI3Kγ by Ras and GPCRs

This study identifies molecular differences between p110γ-p84 and p110γ-p101 complexes that explain their differential activation by GPCRs and Ras.

ATP-competitive and allosteric inhibitors induce differential conformational changes at the auto-inhibitory interface of Akt

This study investigates how ATP-competitive and allosteric inhibitors induce different conformational changes in Akt's auto-inhibitory interface across various phosphorylation states.

PKD autoinhibition in trans regulates activation loop autophosphorylation in cis

This study shows PKD is regulated by trans-autoinhibition followed by cis autophosphorylation, switching the kinase on by preventing re-autoinhibition.

Oncogenic mutations of PIK3CA lead to increased membrane recruitment driven by reorientation of the ABD, p85 and C-terminus

This study identifies unique regulatory mechanisms by which oncogenic PIK3CA mutations enhance PI3K membrane recruitment and activation through structural reorientations.

Dynamics of allosteric regulation of the phospholipase C-γ isozymes upon recruitment to membranes

This study shows that PLC-gamma1 becomes active upon binding to FGFR1 kinase domain and membrane-bound PIP2, with an oncogenic mutation enhancing this activation.

Activation of the essential kinase PDK1 by phosphoinositide-driven autophosphorylation

This study reveals how PDK1 is activated by phosphoinositides through autophosphorylation via a dimer mechanism and PH domain regulation.

Palmitoylation targets the Calcineurin phosphatase to the Phosphatidylinositol 4-kinase complex at the plasma membrane

This study identifies palmitoylation as a mechanism that localizes CNA{beta}1 to the plasma membrane and Golgi, enabling its interaction with the PI4KA complex and regulating PI4P production.

Structure of the phosphoinositide 3-kinase p110γ-p101 complex reveals molecular mechanism of GPCR activation

The paper reports the cryo-EM structure of the p110γ-p101 complex, revealing how GPCR activation is mediated through interactions with Gβγ and identifying potential therapeutic targets.

Biochemical insight into novel Rab-GEF activity of the mammalian TRAPPIII complex

This study investigates the GEF activity of TRAPPIII and TRAPPII complexes toward Rab GTPases using biochemical and structural methods, revealing Rab specificity and membrane interaction mechanisms.

HDX-MS optimized approach to characterize nanobodies as tools for biochemical and structural studies of class IB phosphoinositide 3-kinases

This paper uses HDX-MS to characterize nanobodies targeting PI3K{gamma} complexes, identifying epitopes and functional effects on lipid kinase activity and GPCR activation.

In vitro reconstitution of Sgk3 activation by phosphatidylinositol-3-phosphate

This study shows that Sgk3 is activated by PI3P through conformational changes and reconstitutes this activation in vitro using Vps34-mediated PI3P synthesis on liposomes.

The middle lipin (M-Lip) domain is a new dimeric protein fold that binds membranes

The paper identifies the M-Lip domain as a novel dimeric protein fold that binds membranes and is essential for lipin function.

Crystal structure of a bacterial CNNM magnesium transporter

The paper determines the crystal structure of an archaeal CNNM protein bound to Mg2+-ATP, revealing its transmembrane fold and suggesting it functions as a cation transporter.

Disease related mutations in PI3Kγ disrupt regulatory C-terminal dynamics and reveals a path to selective inhibitors

This study investigates how mutations in PI3Kγ affect its regulatory dynamics and identifies a strategy for developing selective inhibitors.

Activation of phospholipase C β by Gβγ and Gαq involves C-terminal rearrangement to release auto-inhibition

This study investigates how Gβγ and Gαq activate PLCβ by inducing structural changes in its C-terminal domain, leading to increased hydrolase activity.

Defining how oncogenic and developmental mutations of PIK3R1 alter the regulation of class IA phosphoinositide 3-kinases

This study investigates how mutations in PIK3R1 affect class IA PI3K regulation, finding that oncogenic mutations hyper-activate p110 while developmental mutations reduce RTK sensitivity.

Characterisation of the c10orf76-PI4KB complex, and its necessity for Golgi PI4P levels and enterovirus replication

This study characterizes the c10orf76-PI4KB complex, showing its role in maintaining Golgi PI4P levels and enabling enterovirus replication.