J. H. Hurley

Mechanism and cellular function of direct membrane binding by the ESCRT and ERES-associated Ca2+-sensor ALG-2

This study investigates how ALG-2 binds membranes and proteins in a Ca2+-dependent manner, revealing its role in membrane repair and ERES function.

A Flat Protein Complex Shapes Rough ER Membrane Sheets

The paper identifies Sigma-1 receptor as a factor shaping rough ER sheets through proteomics and imaging, showing its role in membrane flattening.

Structural pathway for class III PI 3-kinase activation by the myristoylated GTP-binding pseudokinase VPS15

This study maps the structural pathway of class III PI 3-kinase activation by showing how N-myristoylation of VPS15 stabilizes the inactive conformation and how GTP binding promotes activation.

A RAB7A Phosphoswitch Coordinates Rubicon Homology Protein Regulation of PINK1/Parkin-Dependent Mitophagy

This study identifies a RAB7A phosphoswitch regulated by TBK1 that modulates Rubicon and Pacer interactions to control PINK1/Parkin-dependent mitophagy.

Tau fibrils induce nanoscale membrane damage and nucleate cytosolic tau at lysosomes

This study shows tau fibrils enter cells via endocytosis, accumulate in lysosomes, cause membrane damage, and nucleate cytosolic tau at lysosomes.

Three-step docking by WIPI2, ATG16L1 and ATG3 delivers LC3 to the phagophore

The paper identifies three sequential steps by which the ATG12-ATG5-ATG16L1 complex delivers LC3 to the phagophore via WIPI2, ATG16L1, and ATG3.

Structure and activation of the human autophagy-initiating ULK1C:PI3KC3-C1 supercomplex

The paper determines the cryo-EM structure of the human ULK1C core and its complex with PI3KC3-C1, revealing structural changes that suggest a mechanism for autophagy initiation through supercomplex formation.

Kinetic investigation reveals an HIV-1 Nef-dependent increase in AP-2 recruitment and productivity at endocytic sites

The paper investigates how HIV-1 Nef enhances AP-2 recruitment and productivity at endocytic sites through clathrin-mediated endocytosis.

Organization of Upstream ESCRT Machinery at the HIV-1 Budding Site

This study uses molecular dynamics simulations to investigate how ESCRT-I and ESCRT-II proteins interact with HIV-1 Gag lattice at the budding site, revealing their role in modulating membrane curvature and enabling scission.

Structural basis for mTORC1-dependent regulation of the lysosomal and autophagic transcription factor TFEB

This paper determines the structural basis of mTORC1-dependent phosphorylation of TFEB using cryo-EM, revealing how TFEB is presented to mTORC1 for phosphorylation through a unique RagC GDP-dependent mechanism.

Structural basis for ATG9A recruitment to the ULK1 complex in mitophagy initiation

The paper determines the structure of ATG9A's C-terminal tail interacting with the ULK1 complex's ATG13:ATG101 HORMA dimer, revealing how this interaction facilitates mitophagy.

Structural basis for FLCN RagC GAP activation in MiT-TFE substrate-selective mTORC1 regulation

The paper determines the cryo-EM structure of the active FLCN complex, revealing how it selectively regulates mTORC1 substrates TFEB and TFE3.

Self-assembly and structure of a clathrin-independent AP-1:Arf1 tubular membrane coat

The paper determines the structure of an AP-1:Arf1 tubular membrane coat formed without clathrin, revealing its self-assembly mechanism and role in HIV-1 immune evasion.

Membrane curvature sensing and stabilization by the autophagic LC3 lipidation machinery

The paper investigates how the LC3 lipidation machinery interacts with curved membranes during autophagy initiation, showing that ATG12-5-16L1 stabilizes membrane curvature.

In vitro reconstitution of calcium-dependent recruitment of the human ESCRT machinery in lysosomal membrane repair

This study reconstitutes the Ca2+-dependent recruitment of the human ESCRT machinery to lysosomal membranes in vitro, identifying ALG-2 as a key mediator of this process.

Friction-driven membrane scission by the human ESCRT-III proteins CHMP1B and IST1

This study shows that CHMP1B and IST1 can sever membranes through a friction-driven mechanism, requiring constriction and extensional force, but not VPS4 or spastin.

Structural Basis for Membrane Recruitment of ATG16L1 by WIPI2 in Autophagy

This study determines the crystal structure of WIPI2 interacting with ATG16L1, revealing the molecular mechanism of ATG16L1 recruitment to the phagophore and its role in autophagy initiation.

Structural basis for the ARF GAP activity and specificity of the C9orf72 complex

The paper determines the cryo-EM structure of the C9orf72 complex bound to ARF1-GDP-BeF3, revealing its specific GAP activity toward ARF1 and lower efficiency toward RAB8A.

Reconstitution of cargo-induced LC3 lipidation in mammalian selective autophagy

This study investigates how different cargo receptors stimulate LC3 lipidation in selective autophagy using GUVs and shows varying requirements for autophagy core complexes.

Crystallographic molecular replacement using an in silico-generated search model of SARS-CoV-2 ORF8

The paper assesses whether an in silico-predicted structure of SARS-CoV-2 ORF8 can serve as a molecular replacement search model, finding it successful in solving the phase problem.

Structure of SARS-CoV-2 ORF8, a rapidly evolving coronavirus protein implicated in immune evasion

The paper determines the crystal structure of SARS-CoV-2 ORF8, revealing unique dimerization interfaces that may enable immune evasion.

Structural mechanism for amino acid-dependent Rag GTPase switching by SLC38A9

This paper reveals how SLC38A9 destabilizes the lysosomal FLC complex to promote Rag dimer activation by disrupting the GAP activity toward RagC.

The autophagy adaptor NDP52 and the FIP200 coiled-coil allosterically activate ULK1 complex membrane recruitment

This study shows NDP52 allosterically activates ULK1 complex membrane recruitment via FIP200 coiled-coil conformational changes, essential for xenophagy and mitophagy.

A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission

This study determines the structure of human ESCRT-I and shows it forms a helical assembly that scaffolds and mechanically drives membrane scission during HIV-1 budding.

Structural basis for autophagy inhibition by the human Rubicon-Rab7 complex

This study determines the crystal structure of the Rubicon RH domain bound to Rab7-GTP, revealing its mechanism of autophagy inhibition and validating it as a therapeutic target.

Structure of the lysosomal SCARF (L-SCARF) complex, an Arf GAP haploinsufficient in ALS and FTD

The paper determines the structure of the L-SCARF complex, showing it functions as an Arf GAP and explains its role in ALS and FTD.

ULK complex organization in autophagy by a C-shaped FIP200 N-terminal domain dimer

The paper identifies the C-shaped dimeric structure of FIP200's N-terminal domain and its role in organizing the ULK complex by directly binding ATG13.

A PI3K-WIPI2 positive feedback loop allosterically activates LC3 lipidation in autophagy

The paper reconstitutes autophagy-related reactions and shows that a positive feedback loop between PI3KC3-C1 and WIPI2 accelerates LC3 lipidation.

Structural Pathway for Allosteric Activation of the Autophagic PI 3-Kinase Complex I

The paper maps structural changes in PI3KC3-C1 activation by NRBF2 MIT domains using cryo-EM, showing how binding leads to conformational shifts enabling enzymatic activity.

Allosteric activation of the nitric oxide receptor soluble guanylate cyclase mapped by cryo-electron microscopy