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Insights into links between autophagy and the ubiquitin system from the structure of LC3B bound to the LIR motif from the E3 ligase NEDD4.

Qiu Y, Zheng Y, Wu KP, Schulman BA
Protein Sci 26 1674-1680 (2017)
Cited: 14 times
EuropePMC logo PMID: 28470758

Abstract

Members of the LC3/GABARAP family of ubiquitin-like proteins function during autophagy by serving as membrane linked protein-binding platforms. Their C-termini are physically attached to membranes through covalent linkage to primary amines on lipids such as phosphatidylethanolamine, while their ubiquitin-like fold domains bind "LIR" (LC3-Interacting Region) sequences found within an extraordinarily diverse array of proteins including regulators of autophagy, adaptors that recruit ubiquitinated cargoes to be degraded, and even proteins controlling processes at membranes that are not associated with autophagy. Recently, LC3/GABARAP proteins were found to bind the ubiquitin E3 ligase NEDD4 to influence ubiquitination associated with autophagy in human cell lines. Here, we use purified recombinant proteins to define LC3B interactions with a specific LIR sequence from NEDD4, present a crystal structure showing atomic details of the interaction, and show that LC3B-binding can steer intrinsic NEDD4 E3 ligase activity. The data provide detailed molecular insights underlying recruitment of an E3 ubiquitin ligase to phagophores during autophagy.

Articles - 5v4k mentioned but not cited (2)

  1. Insights into links between autophagy and the ubiquitin system from the structure of LC3B bound to the LIR motif from the E3 ligase NEDD4. Qiu Y, Zheng Y, Wu KP, Schulman BA. Protein Sci 26 1674-1680 (2017)
  2. Recognition motifs for importin 4 [(L)PPRS(G/P)P] and importin 5 [KP(K/Y)LV] binding, identified by bio-informatic simulation and experimental in vitro validation. Panagiotopoulos AA, Kalyvianaki K, Tsodoulou PK, Darivianaki MN, Dellis D, Notas G, Daskalakis V, Theodoropoulos PA, Panagiotidis CΑ, Castanas E, Kampa M. Comput Struct Biotechnol J 20 5952-5961 (2022)


Reviews citing this publication (4)

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  2. Structure and Dynamics in the ATG8 Family From Experimental to Computational Techniques. Sora V, Kumar M, Maiani E, Lambrughi M, Tiberti M, Papaleo E. Front Cell Dev Biol 8 420 (2020)
  3. A Small Viral PPxY Peptide Motif To Control Antiviral Autophagy. Montespan C, Wiethoff CM, Wodrich H. J Virol 91 (2017)
  4. Reciprocal Regulation of Hippo and WBP2 Signalling-Implications in Cancer Therapy. Lim YX, Lin H, Seah SH, Lim YP. Cells 10 (2021)

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  1. Molecular determinants regulating selective binding of autophagy adapters and receptors to ATG8 proteins. Wirth M, Zhang W, Razi M, Nyoni L, Joshi D, O'Reilly N, Johansen T, Tooze SA, Mouilleron S. Nat Commun 10 2055 (2019)
  2. Epithelial-derived gasdermin D mediates nonlytic IL-1β release during experimental colitis. Bulek K, Zhao J, Liao Y, Rana N, Corridoni D, Antanaviciute A, Chen X, Wang H, Qian W, Miller-Little WA, Swaidani S, Tang F, Willard BB, McCrae K, Kang Z, Dubyak GR, Cominelli F, Simmons A, Pizarro TT, Li X. J Clin Invest 130 4218-4234 (2020)
  3. Astrocytes and neurons produce distinct types of polyglucosan bodies in Lafora disease. Augé E, Pelegrí C, Manich G, Cabezón I, Guinovart JJ, Duran J, Vilaplana J. Glia 66 2094-2107 (2018)
  4. AlphaFold2-multimer guided high-accuracy prediction of typical and atypical ATG8-binding motifs. Ibrahim T, Khandare V, Mirkin FG, Tumtas Y, Bubeck D, Bozkurt TO. PLoS Biol 21 e3001962 (2023)
  5. The crystal structure of the FAM134B-GABARAP complex provides mechanistic insights into the selective binding of FAM134 to the GABARAP subfamily. Zhao J, Li Z, Li J. FEBS Open Bio 12 320-331 (2022)
  6. AGXT2L1 is downregulated in carcinomas of the digestive system. Deng Y, Wu L, Ding Q, Yu H. Oncol Lett 20 1318-1326 (2020)
  7. NEDD4 E3 ubiquitin protein ligase serves an important role in cutaneous melanoma occurrence and development. Cheng F, Cheng Y, Zhao X, An L, Yang L, Li Z, Zhang L, He R. Exp Ther Med 22 1382 (2021)
  8. Suppressor of Cytokine Signaling 2 Regulates Retinal Pigment Epithelium Metabolism by Enhancing Autophagy. Liu XY, Lu R, Chen J, Wang J, Qian HM, Chen G, Wu RH, Chi ZL. Front Neurosci 15 738022 (2021)


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