Publications

bioRxiv Recent 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010- earlier

Recent Work

  • The transcription factor TFEB is a master regulator of lysosomal biogenesis and autophagy¹. The phosphorylation of TFEB by the mechanistic target of rapamycin complex 1 (mTORC1)^(2-5) is unique in its mTORC1 substrate recruitment mechanism, which is strictly dependent on the amino acid-mediated activation of the RagC GTPase activating protein FLCN^(6,7). […]
  • How the highly curved phagophore membrane is stabilized during autophagy initiation is a major open question in autophagosome biogenesis. Here, we use in vitro reconstitution on membrane nanotubes and molecular dynamics simulations to investigate how core autophagy proteins in the LC3 (Microtubule-associated proteins 1A/1B light chain 3) lipidation cascade interact […]
  • Small GTPases act as molecular switches and control numerous cellular processes by their binding and hydrolysis of guanosine triphosphate (GTP). The activity of small GTPases is coordinated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). Recent structural and functional studies have characterized a subset of GAPs whose […]
  • The adaptor protein (AP) complexes not only form the inner layer of clathrin coats but also have clathrin-independent roles in membrane traffic whose mechanisms are unknown. HIV-1 Nef hijacks AP-1 to sequester major histocompatibility complex class I (MHC-I), evading immune detection. We found that AP-1:Arf1:Nef:MHC-I forms a coat on tubulated […]
  • Stimulator of interferon genes (STING) functions downstream of cyclic GMP-AMP synthase in DNA sensing or as a direct receptor for bacterial cyclic dinucleotides and small molecules to activate immunity during infection, cancer and immunotherapy^(1-10). Precise regulation of STING is essential to ensure balanced immune responses and prevent detrimental autoinflammation^(11-16). After […]

2020

Fromm SA, Lawrence RE, Hurley JH. Structural mechanism for amino acid-dependent Rag GTPase nucleotide state switching by SLC38A9. Nat Struct Mol Biol. 2020 Aug 31. doi: 10.1038/s41594-020-0490-9. Epub ahead of print. PMID: 32868926.

Su MY, Fromm SA, Zoncu R, Hurley JH. Structure of the C9orf72 ARF GAP complex that is haploinsufficient in ALS and FTD. Nature. 2020 Sep;585(7824):251-255. doi: 10.1038/s41586-020-2633-x. Epub 2020 Aug 26. PMID: 32848248.

Shi X, Chang C, Yokom AL, Jensen LE, Hurley JH. The autophagy adaptor NDP52 and the FIP200 coiled-coil allosterically activate ULK1 complex membrane recruitment. Elife. 2020 Aug 10;9:e59099. doi: 10.7554/eLife.59099. PMID: 32773036; PMCID: PMC7447430.

Bhargava HK, Tabata K, Byck JM, Hamasaki M, Farrell DP, Anishchenko I, DiMaio F, Im YJ, Yoshimori T, Hurley JH. Structural basis for autophagy inhibition by the human Rubicon-Rab7 complex. Proc Natl Acad Sci U S A. 2020 Jul 21;117(29):17003-17010. doi: 10.1073/pnas.2008030117. Epub 2020 Jul 6. PMID: 32632011; PMCID: PMC7382272.

Shi, X., Yokom, A. L., Wang, C., Young, L. N., Youle, R. J., & Hurley, J. H. (2020). ULK complex organization in autophagy by a C-shaped FIP200 N-terminal domain dimerThe Journal of cell biology219(7), e201911047. https://doi.org/10.1083/jcb.201911047

Fracchiolla, D., Chang, C., Hurley, J. H., & Martens, S. (2020). A PI3K-WIPI2 positive feedback loop allosterically activates LC3 lipidation in autophagyThe Journal of cell biology219(7), e201912098. https://doi.org/10.1083/jcb.201912098

Flower, T. G., Takahashi, Y., Hudait, A., Rose, K., Tjahjono, N., Pak, A. J., Yokom, A. L., Liang, X., Wang, H. G., Bouamr, F., Voth, G. A., & Hurley, J. H. (2020). A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scissionNature structural & molecular biology27(6), 570–580. https://doi.org/10.1038/s41594-020-0426-4

Prinz, W. A., & Hurley, J. H. (2020). A firehose for phospholipidsThe Journal of cell biology219(5), e202003132. https://doi.org/10.1083/jcb.202003132

2019

Lawrence, R. E., Fromm, S. A., Fu, Y., Yokom, A. L., Kim, D. J., Thelen, A. M., Young, L. N., Lim, C. Y., Samelson, A. J., Hurley, J. H., & Zoncu, R. (2019). Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complexScience (New York, N.Y.)366(6468), 971–977. https://doi.org/10.1126/science.aax0364

Young, L. N., Goerdeler, F., & Hurley, J. H. (2019). Structural pathway for allosteric activation of the autophagic PI 3-kinase complex IProceedings of the National Academy of Sciences of the United States of America116(43), 21508–21513. https://doi.org/10.1073/pnas.1911612116

Buffalo, C. Z., Iwamoto, Y., Hurley, J. H., & Ren, X. (2019). How HIV Nef Proteins Hijack Membrane Traffic To Promote InfectionJournal of virology93(24), e01322-19. https://doi.org/10.1128/JVI.01322-19

Horst, B. G., Yokom, A. L., Rosenberg, D. J., Morris, K. L., Hammel, M., Hurley, J. H., & Marletta, M. A. (2019). Allosteric activation of the nitric oxide receptor soluble guanylate cyclase mapped by cryo-electron microscopyeLife8, e50634. https://doi.org/10.7554/eLife.50634

Buffalo, C. Z., Stürzel, C. M., Heusinger, E., Kmiec, D., Kirchhoff, F., Hurley, J. H., & Ren, X. (2019). Structural Basis for Tetherin Antagonism as a Barrier to Zoonotic Lentiviral TransmissionCell host & microbe26(3), 359–368.e8. https://doi.org/10.1016/j.chom.2019.08.002

Turco, E., Witt, M., Abert, C., Bock-Bierbaum, T., Su, M. Y., Trapannone, R., Sztacho, M., Danieli, A., Shi, X., Zaffagnini, G., Gamper, A., Schuschnig, M., Fracchiolla, D., Bernklau, D., Romanov, J., Hartl, M., Hurley, J. H., Daumke, O., & Martens, S. (2019). How RB1CC1/FIP200 claws its way to autophagic engulfment of SQSTM1/p62-ubiquitin condensatesAutophagy15(8), 1475–1477. https://doi.org/10.1080/15548627.2019.1615306

Chang, C., Young, L. N., & Hurley, J. H. (2019). The BARA necessities of PtdIns 3-kinase activation in autophagyAutophagy15(6), 1122–1123. https://doi.org/10.1080/15548627.2019.1596501

Turco, E., Witt, M., Abert, C., Bock-Bierbaum, T., Su, M. Y., Trapannone, R., Sztacho, M., Danieli, A., Shi, X., Zaffagnini, G., Gamper, A., Schuschnig, M., Fracchiolla, D., Bernklau, D., Romanov, J., Hartl, M., Hurley, J. H., Daumke, O., & Martens, S. (2019). FIP200 Claw Domain Binding to p62 Promotes Autophagosome Formation at Ubiquitin CondensatesMolecular cell74(2), 330–346.e11. https://doi.org/10.1016/j.molcel.2019.01.035

Brier, L. W., Ge, L., Stjepanovic, G., Thelen, A. M., Hurley, J. H., & Schekman, R. (2019). Regulation of LC3 lipidation by the autophagy-specific class III phosphatidylinositol-3 kinase complexMolecular biology of the cell30(9), 1098–1107. https://doi.org/10.1091/mbc.E18-11-0743

Hurley, J. H., & Johannes, L. (2019). Retro Styles for Vesicle CoatsBiochemistry58(6), 433–434. https://doi.org/10.1021/acs.biochem.8b01271

Chang, C., Young, L. N., Morris, K. L., von Bülow, S., Schöneberg, J., Yamamoto-Imoto, H., Oe, Y., Yamamoto, K., Nakamura, S., Stjepanovic, G., Hummer, G., Yoshimori, T., & Hurley, J. H. (2019). Bidirectional Control of Autophagy by BECN1 BARA Domain DynamicsMolecular cell73(2), 339–353.e6. https://doi.org/10.1016/j.molcel.2018.10.035

2018

Schöneberg, J., Pavlin, M. R., Yan, S., Righini, M., Lee, I. H., Carlson, L. A., Bahrami, A. H., Goldman, D. H., Ren, X., Hummer, G., Bustamante, C., & Hurley, J. H. (2018). ATP-dependent force generation and membrane scission by ESCRT-III and Vps4Science (New York, N.Y.)362(6421), 1423–1428. https://doi.org/10.1126/science.aat1839

Schulze-Gahmen, U., & Hurley, J. H. (2018). Structural mechanism for HIV-1 TAR loop recognition by Tat and the super elongation complexProceedings of the National Academy of Sciences of the United States of America115(51), 12973–12978. https://doi.org/10.1073/pnas.1806438115

Hurley, J. H., & Cada, A. K. (2018). Inside job: how the ESCRTs release HIV-1 from infected cellsBiochemical Society transactions46(5), 1029–1036. https://doi.org/10.1042/BST20180019

Lawrence, R. E., Cho, K. F., Rappold, R., Thrun, A., Tofaute, M., Kim, D. J., Moldavski, O., Hurley, J. H., & Zoncu, R. (2018). A nutrient-induced affinity switch controls mTORC1 activation by its Rag GTPase-Ragulator lysosomal scaffoldNature cell biology20(9), 1052–1063. https://doi.org/10.1038/s41556-018-0148-6

Morris, K. L., Buffalo, C. Z., Stürzel, C. M., Heusinger, E., Kirchhoff, F., Ren, X., & Hurley, J. H. (2018). HIV-1 Nefs Are Cargo-Sensitive AP-1 Trimerization Switches in Tetherin DownregulationCell174(3), 659–671.e14. https://doi.org/10.1016/j.cell.2018.07.004

Lin, M. G., Schöneberg, J., Davies, C. W., Ren, X., & Hurley, J. H. (2018). The dynamic Atg13-free conformation of the Atg1 EAT domain is required for phagophore expansionMolecular biology of the cell29(10), 1228–1237. https://doi.org/10.1091/mbc.E17-04-0258

Gardner, B. M., Castanzo, D. T., Chowdhury, S., Stjepanovic, G., Stefely, M. S., Hurley, J. H., Lander, G. C., & Martin, A. (2018). The peroxisomal AAA-ATPase Pex1/Pex6 unfolds substrates by processive threadingNature communications9(1), 135. https://doi.org/10.1038/s41467-017-02474-4

2017

Stjepanovic, G., Baskaran, S., Lin, M. G., & Hurley, J. H. (2017). Unveiling the role of VPS34 kinase domain dynamics in regulation of the autophagic PI3K complexMolecular & cellular oncology4(6), e1367873. https://doi.org/10.1080/23723556.2017.1367873

Su, M. Y., Morris, K. L., Kim, D. J., Fu, Y., Lawrence, R., Stjepanovic, G., Zoncu, R., & Hurley, J. H. (2017). Hybrid Structure of the RagA/C-Ragulator mTORC1 Activation ComplexMolecular cell68(5), 835–846.e3. https://doi.org/10.1016/j.molcel.2017.10.016

Bahrami, A. H., Lin, M. G., Ren, X., Hurley, J. H., & Hummer, G. (2017). Scaffolding the cup-shaped double membrane in autophagyPLoS computational biology13(10), e1005817. https://doi.org/10.1371/journal.pcbi.1005817

Stjepanovic, G., Baskaran, S., Lin, M. G., & Hurley, J. H. (2017). Vps34 Kinase Domain Dynamics Regulate the Autophagic PI 3-Kinase ComplexMolecular cell67(3), 528–534.e3. https://doi.org/10.1016/j.molcel.2017.07.003

Mandadapu, K. K., & Hurley, J. H. (2017). Friction at the BAR Leads to Membrane BreakupCell170(1), 14–16. https://doi.org/10.1016/j.cell.2017.06.027

Hurley, J. H., & Young, L. N. (2017). Mechanisms of Autophagy InitiationAnnual review of biochemistry86, 225–244. https://doi.org/10.1146/annurev-biochem-061516-044820

Qi, S., Li, Z., Schulze-Gahmen, U., Stjepanovic, G., Zhou, Q., & Hurley, J. H. (2017). Structural basis for ELL2 and AFF4 activation of HIV-1 proviral transcriptionNature communications8, 14076. https://doi.org/10.1038/ncomms14076

Tooze, S. A., & Hurley, J. H. (2017). Molecular Mechanisms of Autophagy-Part B. Journal of molecular biology429(4), 455–456. https://doi.org/10.1016/j.jmb.2017.01.009

Schöneberg, J., Lee, I. H., Iwasa, J. H., & Hurley, J. H. (2017). Reverse-topology membrane scission by the ESCRT proteinsNature reviews. Molecular cell biology18(1), 5–17. https://doi.org/10.1038/nrm.2016.121

2016

Schulze-Gahmen U, Echeverria I, Stjepanovic G, Bai Y, Lu H, Schneidman-Duhovny D, Doudna JA, Zhou Q, Sali A, Hurley JH. Insights into HIV-1 proviral transcription from integrative structure and dynamics of the Tat:AFF4:P-TEFb:TAR complex. Elife. 2016 Oct 12;5:e15910. doi: 10.7554/eLife.15910. PMID: 27731797; PMCID: PMC5072841.

Hurley JH, Nogales E. Next-generation electron microscopy in autophagy research. Curr Opin Struct Biol. 2016 Dec;41:211-216. doi: 10.1016/j.sbi.2016.08.006. Epub 2016 Sep 8. PMID: 27614295; PMCID: PMC5154772.

Young LN, Cho K, Lawrence R, Zoncu R, Hurley JH. Dynamics and architecture of the NRBF2-containing phosphatidylinositol 3-kinase complex I of autophagy. Proc Natl Acad Sci U S A. 2016 Jul 19;113(29):8224-9. doi: 10.1073/pnas.1603650113. Epub 2016 Jul 6. PMID: 27385829; PMCID: PMC4961193.