Structure and flexibility of the endosomal Vps34 complex reveals the basis of its function on membranes

Rostislavleva, Ksenia; Soler, Nicolas; Ohashi, Yohei; Zhang, Lufei; Pardon, Els; Burke, John E.; Masson, Glenn R.; Johnson, Chris; Steyaert, Jan; Ktistakis, Nicholas T.; Williams, Roger L.

doi:10.1126/science.aac7365

Cited by 238

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Structure and flexibility of the endosomal Vps34 complex reveals the basis of its function on membranes

Rostislavleva, Ksenia, Soler, Nicolas, Ohashi, Yohei, Zhang, Lufei, Pardon, Els, Burke, John E., Masson, Glenn R., Johnson, Chris, Steyaert, Jan, Ktistakis, Nicholas T., Williams, Roger L.·2015·Science

DOI 10.1126/science.aac7365PMC PMC4601532

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Abstract

Opening up Vps34 protein complexes: During intracellular membrane trafficking, large protein complexes regulate and adapt the activity of signal transducer enzymes such as the class III phosphatidylinositol 3-kinase Vps34. These large enzyme complexes are present in all eukaryotic cells, having widespread importance in neurodegeneration, aging, and cancer; however, a structural understanding has been lacking. Rostislavleva et al. provide atomic-resolution insights into the structures of the Vps34-containing protein complexes required for autophagy, endocytic sorting, and cytokinesis. The V-shaped complexes can undergo opening motions, which allows them to adapt to and phosphorylate membranes. Science , this issue p. 10.1126/science.aac7365

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“and ATG9A deficiency in the mouse brain causes axonspecific lesions including neuronal circuit dysgenesis [800].”
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Phaser crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612
Two Distinct Vps34 Phosphatidylinositol 3–Kinase Complexes Function in Autophagy and Carboxypeptidase Y Sorting in Saccharomyces cerevisiae
Kihara, A., Noda, T., Ishihara, N., & Ohsumi, Y. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.3.519 · Cited by 1,004
Akt-Mediated Regulation of Autophagy and Tumorigenesis Through Beclin 1 Phosphorylation
Wang, R. C., Wei, Y., An, Z., Zou, Z., Xiao, G., Bhagat, G., White, M., Reichelt, J., & Levine, B. (2012) · Science · doi:10.1126/science.1225967 · Cited by 728
DAP‐kinase‐mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl‐XL and induction of autophagy
Zalckvar, E., Berissi, H., Mizrachy, L., Idelchuk, Y., Koren, I., Eisenstein, M., Sabanay, H., Pinkas‐Kramarski, R., & Kimchi, A. (2009) · The EMBO Reports · doi:10.1038/embor.2008.246 · Cited by 592
A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy
Ronan, B., Flamand, O., Vescovi, L., Dureuil, C., Durand, L., Fassy, F., Bachelot, M.-F., Lamberton, A., Mathieu, M., Bertrand, T., et al. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1681 · Cited by 500
Oncogenic mutations mimic and enhance dynamic events in the natural activation of phosphoinositide 3-kinase p110α ( PIK3CA )
Burke, J. E., Perisic, O., Masson, G. R., Vadas, O., & Williams, R. L. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1205508109 · Cited by 300
Self-citation
Autophagosome targeting and membrane curvature sensing by Barkor/Atg14(L)
Fan, W., Nassiri, A., & Zhong, Q. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016472108 · Cited by 285

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Research works printed but not linked: 59

Herman P. K., Emr S. D., Characterization of VPS34, a gene required for vacuolar protein sorting and vacuole segregation in Saccharomyces cerevisiae. Mol. Cell. Biol. 10, 6742–6754 (1990). 2247081
10.1126/science.8385367 · DOI · Paper page
10.1371/journal.pone.0076405 · DOI · Paper page
10.1083/jcb.201304123 · DOI · Paper page
10.1016/j.yexcr.2010.07.008 · DOI
10.1042/BJ20140889 · DOI · Paper page
10.1038/onc.2014.454 · DOI
10.4049/jimmunol.1100710 · DOI
10.15252/embj.201590992 · DOI
10.1371/journal.pgen.1004626 · DOI
10.1016/j.leukres.2015.02.008 · DOI
10.1038/ncb3053 · DOI · Paper page
10.1038/nprot.2014.039 · DOI
10.1021/bi900621w · DOI
10.1074/jbc.M112.348250 · DOI
10.1126/science.1184429 · DOI
10.7554/eLife.05115 · DOI
10.1002/j.1460-2075.1993.tb05867.x · DOI
10.1002/j.1460-2075.1991.tb04981.x · DOI
10.1098/rstb.2012.0054 · DOI
10.1074/jbc.M111.253435 · DOI
10.4161/auto.1.1.1542 · DOI
10.1074/jbc.M109263200 · DOI
10.1126/scisignal.2004298 · DOI
10.1073/pnas.1217692110 · DOI
10.1371/journal.pone.0043369 · DOI
10.1038/ncb1426 · DOI · Paper page
10.1016/j.cell.2012.12.016 · DOI
10.1016/j.molcel.2010.05.009 · DOI
10.1038/ncomms1648 · DOI
10.1038/cr.2012.24 · DOI
10.1016/j.cell.2006.04.045 · DOI
10.1371/journal.pone.0086680 · DOI
10.1034/j.1600-0854.2002.30605.x · DOI · Paper page
10.1034/j.1600-0854.2003.00133.x · DOI
10.1128/MCB.01327-13 · DOI
10.1083/jcb.200803137 · DOI · Paper page
10.1016/j.pbiomolbio.2004.07.009 · DOI
10.1107/S0907444910006724 · DOI
10.1107/S0907444909047337 · DOI · Paper page
Vonrhein C., Blanc E., Roversi P., Bricogne G., Automated structure solution with autoSHARP. Methods Mol. Biol. 364, 215–230 (2007). 17172768
10.1107/S0907444909038360 · DOI
10.1093/nar/gki408 · DOI
10.1107/S0907444907050172 · DOI
10.1107/S0907444995008754 · DOI
10.1107/S0907444909052925 · DOI · Paper page
10.1128/jb.173.6.2026-2034.1991 · DOI
10.7554/eLife.05289 · DOI
10.1016/j.cell.2013.08.015 · DOI · Paper page
10.1038/ncb2757 · DOI · Paper page
10.1038/ncomms8215 · DOI
10.4161/auto.6.7.13288 · DOI
10.1038/emboj.2013.189 · DOI
10.1038/cdd.2011.149 · DOI
10.4161/auto.24877 · DOI
10.1016/j.cellsig.2014.02.009 · DOI
10.1038/nature11843 · DOI
Robinson J. S., Klionsky D. J., Banta L. M., Emr S. D., Protein sorting in Saccharomyces cerevisiae: Isolation of mutants defective in the delivery and processing of multiple vacuolar hydrolases. Mol. Cell. Biol. 8, 4936–4948 (1988).3062374
10.1093/bioinformatics/btl461 · DOI

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“Such necroptotic response is exacerbated, rather than blunted, by chemical inhibitors of lysosomal degradation (Goodall et al., 2016), pointing to a non-autophagic role for ATG5, ATG7, and VPS34 in this setting.”
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Ashkenazi, A., Bento, C. F., Ricketts, T., Vicinanza, M., Siddiqi, F., Pavel, M., Squitieri, F., Hardenberg, M. C., Imarisio, S., Menzies, F. M., et al. (2017) · Nature · doi:10.1038/nature22078 · Cited by 357
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Dickson, E. J., & Hille, B. (2019) · Biochemical Journal · doi:10.1042/bcj20180022 · Cited by 254
The diverse and expanding role of mass spectrometry in structural and molecular biology
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Ma, X., Zhang, S., He, L., Rong, Y., Brier, L. W., Sun, Q., Liu, R., Fan, W., Chen, S., Yue, Z., et al. (2017) · Autophagy · doi:10.1080/15548627.2016.1269988 · Cited by 92
Dynamics and architecture of the NRBF2-containing phosphatidylinositol 3-kinase complex I of autophagy
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Authors: Rostislavleva, K., Soler, N., Ohashi, Y., Zhang, L., Pardon, E., Burke, J. E., Masson, G. R., Johnson, C., Steyaert, J., Ktistakis, N. T., & Williams, R. L.
Affiliations: Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Structural Biology Research Center, VIB, B-1050 Brussels, Belgium.
The Babraham Institute, Cambridge, UK.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2015-10-09
Volume: 350
Issue: 6257
ISSN: 0036-8075
1095-9203
DOI: 10.1126/science.aac7365
PMC: PMC4601532
Cited by: 238
References: 7
Language: en
Licence: www.sciencemag.org/about/science-licenses-journal-article-reuse (vor, 366 d)
Funders: MRC (U105184308)
UK Biotechnology and Biological Sciences Research Council (BB/K019155/1)
British Heart Foundation (PG11/109/29247)
FWO (G0C8514N)
Cambridge Overseas Trust
Hercules Foundation Flanders
Cambridge Cancer Center

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Structure and flexibility of the endosomal Vps34 complex reveals the basis of its function on membranes

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