multiprotein complexes


Summary: Macromolecular complexes formed from the association of defined protein subunits.

Top Publications

  1. Flinner N, Ellenrieder L, Stiller S, Becker T, Schleiff E, Mirus O. Mdm10 is an ancient eukaryotic porin co-occurring with the ERMES complex. Biochim Biophys Acta. 2013;1833:3314-3325 pubmed publisher
    ..Strikingly, the presence of Mdm10 coincides with the appearance of the other ERMES components. Mdm10's presence in both unikonts and bikonts indicates an introduction at an early time point in eukaryotic evolution. ..
  2. Menon S, Dibble C, Talbott G, Hoxhaj G, Valvezan A, Takahashi H, et al. Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome. Cell. 2014;156:771-85 pubmed publisher
    ..These findings provide a unifying mechanism by which independent pathways affecting the spatial recruitment of mTORC1 and the TSC complex to Rheb at the lysosomal surface serve to integrate diverse growth signals. ..
  3. Karunakaran V, Wickner W. Fusion proteins and select lipids cooperate as membrane receptors for the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) Vam7p. J Biol Chem. 2013;288:28557-66 pubmed publisher
    ..Acidic lipids allow low concentrations of Vam7p to suffice for fusion; without acidic lipids, the block to fusion is partially bypassed by high concentrations of Vam7p. ..
  4. Lorin S, Tol M, Bauvy C, Strijland A, Poüs C, Verhoeven A, et al. Glutamate dehydrogenase contributes to leucine sensing in the regulation of autophagy. Autophagy. 2013;9:850-60 pubmed publisher
    ..The data suggest a dual mechanism by which glutamate dehydrogenase activity modulates autophagy, i.e., by activating MTORC1 and by limiting the formation of reactive oxygen species. ..
  5. Conn C, Qian S. Nutrient signaling in protein homeostasis: an increase in quantity at the expense of quality. Sci Signal. 2013;6:ra24 pubmed publisher
    ..Our results reveal a mechanistic connection between mTORC1 and protein quality, highlighting the central role of nutrient signaling in growth and aging. ..
  6. Fournier M, Coudert L, Mellaoui S, Adjibade P, Gareau C, Côté M, et al. Inactivation of the mTORC1-eukaryotic translation initiation factor 4E pathway alters stress granule formation. Mol Cell Biol. 2013;33:2285-301 pubmed publisher
    ..This work therefore highlights a novel role of the oncogenic mTORC1-eIF4E pathway, namely, the promotion of formation of antiapoptotic SG. ..
  7. Bar Peled L, Chantranupong L, Cherniack A, Chen W, Ottina K, Grabiner B, et al. A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science. 2013;340:1100-6 pubmed publisher
    ..Thus, we identify a key negative regulator of the Rag GTPases and reveal that, like other mTORC1 regulators, Rag function can be deregulated in cancer. ..
  8. Ingels A, Zhao H, Thong A, Saar M, Valta M, Nolley R, et al. Preclinical trial of a new dual mTOR inhibitor, MLN0128, using renal cell carcinoma tumorgrafts. Int J Cancer. 2014;134:2322-9 pubmed publisher
    ..Our results demonstrated that MLN0128 is superior to temsirolimus in inhibiting primary RCC growth as well as metastases, lending strong support for further clinical development of dual mTOR inhibitors for RCC treatment. ..
  9. Melnik B, Zouboulis C. Potential role of FoxO1 and mTORC1 in the pathogenesis of Western diet-induced acne. Exp Dermatol. 2013;22:311-5 pubmed publisher

More Information


  1. Zhang J, Kim J, Alexander A, Cai S, Tripathi D, Dere R, et al. A tuberous sclerosis complex signalling node at the peroxisome regulates mTORC1 and autophagy in response to ROS. Nat Cell Biol. 2013;15:1186-96 pubmed publisher
    ..These data identify a role for the TSC in responding to ROS at the peroxisome, and identify the peroxisome as a signalling organelle involved in regulation of mTORC1. ..
  2. Yamamoto R, Song K, Yanagisawa H, Fox L, Yagi T, Wirschell M, et al. The MIA complex is a conserved and novel dynein regulator essential for normal ciliary motility. J Cell Biol. 2013;201:263-78 pubmed publisher
    ..The MIA complex appears to regulate I1 dynein and possibly outer arm dyneins, which are both essential for normal motility...
  3. Dibble C, Manning B. Signal integration by mTORC1 coordinates nutrient input with biosynthetic output. Nat Cell Biol. 2013;15:555-64 pubmed publisher
    ..Our expanding understanding of the regulatory network upstream of mTORC1 provides molecular insights into the integrated sensing mechanisms by which diverse cellular signals converge to control cell physiology. ..
  4. Epp N, Ungermann C. The N-terminal domains of Vps3 and Vps8 are critical for localization and function of the CORVET tethering complex on endosomes. PLoS ONE. 2013;8:e67307 pubmed publisher
  5. Knyazev D, Lents A, Krause E, Ollinger N, Siligan C, Papinski D, et al. The bacterial translocon SecYEG opens upon ribosome binding. J Biol Chem. 2013;288:17941-6 pubmed publisher
    ..Thus, the open probability of the channel must be close to unity. To prevent the otherwise lethal proton leak, a closed post-translational conformation of the SecYEG complex bound to a ribosome must exist...
  6. Das J, Chakraborty S, Podder S, Ghosh T. Complex-forming proteins escape the robust regulations of miRNA in human. FEBS Lett. 2013;587:2284-7 pubmed publisher
    ..However, the duplicated complex-forming proteins having a severe effect on organismal fitness are profoundly targeted by miRNA, probably to reduce the chances of dosage imbalance. ..
  7. Petit C, Roczniak Ferguson A, Ferguson S. Recruitment of folliculin to lysosomes supports the amino acid-dependent activation of Rag GTPases. J Cell Biol. 2013;202:1107-22 pubmed publisher
    ..These new findings define the lysosome as a site of action for FLCN and indicate a critical role for FLCN in the amino acid-dependent activation of mTOR via its direct interaction with the RagA/B GTPases. ..
  8. Wang Q, Tiffen J, Bailey C, Lehman M, Ritchie W, Fazli L, et al. Targeting amino acid transport in metastatic castration-resistant prostate cancer: effects on cell cycle, cell growth, and tumor development. J Natl Cancer Inst. 2013;105:1463-73 pubmed publisher
    ..Inhibition of LAT transporters may provide a novel therapeutic target in metastatic castration-resistant prostate cancer, via suppression of mammalian target of rapamycin complex 1 activity and M-phase cell cycle genes. ..
  9. Jans D, Wurm C, Riedel D, Wenzel D, Stagge F, Deckers M, et al. STED super-resolution microscopy reveals an array of MINOS clusters along human mitochondria. Proc Natl Acad Sci U S A. 2013;110:8936-41 pubmed publisher
  10. Humphrey S, Yang G, Yang P, Fazakerley D, Stöckli J, Yang J, et al. Dynamic adipocyte phosphoproteome reveals that Akt directly regulates mTORC2. Cell Metab. 2013;17:1009-20 pubmed publisher
    ..The dynamic phosphoproteome described here contains numerous phosphorylation sites on proteins involved in diverse molecular functions and should serve as a useful functional resource for cell biologists. ..
  11. Demetriades C, Doumpas N, Teleman A. Regulation of TORC1 in response to amino acid starvation via lysosomal recruitment of TSC2. Cell. 2014;156:786-99 pubmed publisher
    ..These data suggest that regulation of TSC2 subcellular localization may be a general mechanism to control its activity and place TSC2 in the amino-acid-sensing pathway to TORC1...
  12. Tsun Z, Bar Peled L, Chantranupong L, Zoncu R, Wang T, Kim C, et al. The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1. Mol Cell. 2013;52:495-505 pubmed publisher
    ..We identify FLCN and its binding partners, FNIP1/2, as Rag-interacting proteins with GAP activity for RagC/D, but not RagA/B. Thus, we reveal a role for RagC/D in mTORC1 activation and a molecular function for the FLCN tumor suppressor. ..
  13. Naito T, Kuma A, Mizushima N. Differential contribution of insulin and amino acids to the mTORC1-autophagy pathway in the liver and muscle. J Biol Chem. 2013;288:21074-81 pubmed publisher
    ..These results suggest that autophagy is differentially regulated by insulin and amino acids in a tissue-dependent manner. ..
  14. Chen C, Kiyan V, Zhylkibayev A, Kazyken D, Bulgakova O, Page K, et al. Autoregulation of the mechanistic target of rapamycin (mTOR) complex 2 integrity is controlled by an ATP-dependent mechanism. J Biol Chem. 2013;288:27019-30 pubmed publisher
    ..Thus, the homeostatic ATP sensor mTOR controls the integrity of mTORC2 and phosphorylation of Akt on the turn motif site. ..
  15. Graham S, Wartosch L, Gray S, Scourfield E, Deane J, Luzio J, et al. Structural basis of Vps33A recruitment to the human HOPS complex by Vps16. Proc Natl Acad Sci U S A. 2013;110:13345-50 pubmed publisher
    ..The Vps33A-Vps16 complex provides a structural framework for studying the association between Sec1/Munc18 proteins and tethering complexes. ..
  16. Marsh J, Hern ndez H, Hall Z, Ahnert S, Perica T, Robinson C, et al. Protein complexes are under evolutionary selection to assemble via ordered pathways. Cell. 2013;153:461-70 pubmed publisher
    ..Together, these results reveal the intimate relationships among protein assembly, quaternary structure, and evolution and demonstrate on a genome-wide scale the biological importance of ordered assembly pathways...
  17. Klinger C, Klute M, Dacks J. Comparative genomic analysis of multi-subunit tethering complexes demonstrates an ancient pan-eukaryotic complement and sculpting in Apicomplexa. PLoS ONE. 2013;8:e76278 pubmed publisher
    ..Overall, we demonstrate reduction of MTCs in Apicomplexa and their ancestors, consistent with modification during, and possibly pre-dating, the move from free-living marine algae to deadly human parasites...
  18. Taylor P. Role of amino acid transporters in amino acid sensing. Am J Clin Nutr. 2014;99:223S-230S pubmed publisher
    ..New opportunities for nutritional therapy may include targeting of AA transporters (or mechanisms that upregulate their expression) to promote protein-anabolic signals for retention or recovery of lean tissue mass. ..
  19. Balderhaar H, Ungermann C. CORVET and HOPS tethering complexes - coordinators of endosome and lysosome fusion. J Cell Sci. 2013;126:1307-16 pubmed publisher
    ..Here, we discuss the general function of both complexes in yeast and in metazoan cells in the context of endosomal biogenesis and maturation...
  20. Fernández Cid A, Riera A, Tognetti S, Herrera M, Samel S, Evrin C, et al. An ORC/Cdc6/MCM2-7 complex is formed in a multistep reaction to serve as a platform for MCM double-hexamer assembly. Mol Cell. 2013;50:577-88 pubmed publisher
    ..Importantly, CDK-dependent phosphorylation of ORC inhibits OCM establishment to ensure once per cell cycle replication. In summary, this work reveals multiple critical mechanisms that redefine our understanding of DNA licensing. ..
  21. Thedieck K, Holzwarth B, Prentzell M, Boehlke C, Kläsener K, Ruf S, et al. Inhibition of mTORC1 by astrin and stress granules prevents apoptosis in cancer cells. Cell. 2013;154:859-74 pubmed publisher
    ..Importantly, we show that in cancer cells, apoptosis suppression during stress depends on astrin. Being frequently upregulated in tumors, astrin is a potential clinically relevant target to sensitize tumors to apoptosis. ..
  22. Dehouck Y, Kwasigroch J, Rooman M, Gilis D. BeAtMuSiC: Prediction of changes in protein-protein binding affinity on mutations. Nucleic Acids Res. 2013;41:W333-9 pubmed publisher
  23. Buster D, Daniel S, Nguyen H, Windler S, Skwarek L, Peterson M, et al. SCFSlimb ubiquitin ligase suppresses condensin II-mediated nuclear reorganization by degrading Cap-H2. J Cell Biol. 2013;201:49-63 pubmed publisher
    ..Therefore, SCF(Slimb)-mediated down-regulation of condensin II is required to maintain proper organization and morphology of the interphase nucleus. ..
  24. Betz C, Stracka D, Prescianotto Baschong C, Frieden M, Demaurex N, Hall M. Feature Article: mTOR complex 2-Akt signaling at mitochondria-associated endoplasmic reticulum membranes (MAM) regulates mitochondrial physiology. Proc Natl Acad Sci U S A. 2013;110:12526-34 pubmed publisher
    ..Thus, mTORC2 is at the core of a MAM signaling hub that controls growth and metabolism. ..
  25. Linares J, Duran A, Yajima T, Pasparakis M, Moscat J, Diaz Meco M. K63 polyubiquitination and activation of mTOR by the p62-TRAF6 complex in nutrient-activated cells. Mol Cell. 2013;51:283-96 pubmed publisher
    ..Interfering with the p62-TRAF6 interaction serves to modulate autophagy and nutrient sensing. ..
  26. Wauson E, Lorente Rodríguez A, Cobb M. Minireview: Nutrient sensing by G protein-coupled receptors. Mol Endocrinol. 2013;27:1188-97 pubmed publisher
    ..This review focuses on an array of findings on sensing amino acids and sweet molecules outside of neurons by this cluster of class C GPCRs and some of the physiologic processes regulated by them. ..
  27. Weber T, Koob S, Heide H, Wittig I, Head B, VAN DER BLIEK A, et al. APOOL is a cardiolipin-binding constituent of the Mitofilin/MINOS protein complex determining cristae morphology in mammalian mitochondria. PLoS ONE. 2013;8:e63683 pubmed publisher
    ..Our findings further assign an intracellular role to a member of the apolipoprotein family in mammals. ..
  28. Castets P, Lin S, Rion N, Di Fulvio S, Romanino K, Guridi M, et al. Sustained activation of mTORC1 in skeletal muscle inhibits constitutive and starvation-induced autophagy and causes a severe, late-onset myopathy. Cell Metab. 2013;17:731-44 pubmed publisher
    ..These findings may open interesting avenues for therapeutic strategies directed toward autophagy-related muscle diseases. ..
  29. Ranjan A, Mizuguchi G, FitzGerald P, Wei D, Wang F, Huang Y, et al. Nucleosome-free region dominates histone acetylation in targeting SWR1 to promoters for H2A.Z replacement. Cell. 2013;154:1232-45 pubmed publisher
  30. Das R, Melo J, Thondamal M, Morton E, Cornwell A, Crick B, et al. The homeodomain-interacting protein kinase HPK-1 preserves protein homeostasis and longevity through master regulatory control of the HSF-1 chaperone network and TORC1-restricted autophagy in Caenorhabditis elegans. PLoS Genet. 2017;13:e1007038 pubmed publisher
    ..HPK-1 therefore provides a promising intervention point for pharmacological agents targeting the protein homeostasis system as a means of preserving robust longevity. ..
  31. Hu J, Che L, Li L, Pilo M, Cigliano A, Ribback S, et al. Co-activation of AKT and c-Met triggers rapid hepatocellular carcinoma development via the mTORC1/FASN pathway in mice. Sci Rep. 2016;6:20484 pubmed publisher
    ..Suppression of mTORC1 and/or FASN might be highly detrimental for the growth of human HCC subsets characterized by concomitant induction of the AKT and c-Met cascades. ..
  32. Chen D, Huang Y, Ruan Y, Shen W. The evolutionary landscape of PRC1 core components in green lineage. Planta. 2016;243:825-46 pubmed publisher
    ..Plant LHP1 as the homolog of non-PRC1 protein HP1 was recruited to fulfill the role of Pc counterpart. Gene duplication followed by functional divergence makes a great contribution to evolutionary progress of PRC1 in green plants. ..
  33. Kim K, Qiang L, Hayden M, Sparling D, Purcell N, Pajvani U. mTORC1-independent Raptor prevents hepatic steatosis by stabilizing PHLPP2. Nat Commun. 2016;7:10255 pubmed publisher
    ..These data suggest that the balance of free and mTORC1-associated Raptor governs hepatic lipid accumulation, and uncover the potentially therapeutic role of PHLPP2 activators in non-alcoholic fatty liver disease. ..
  34. Mahmoud S, Planes M, Cabedo M, Trujillo C, Rienzo A, Caballero Molada M, et al. TOR complex 1 regulates the yeast plasma membrane proton pump and pH and potassium homeostasis. FEBS Lett. 2017;591:1993-2002 pubmed publisher
    ..Tco89 does not affect Pma1 activity but activates K+ transport. ..
  35. Singleton M. Getting to the heart of an unusual kinetochore. Open Biol. 2016;6:160040 pubmed publisher
    ..Two recent studies provide new structural insights into the formation of this complex, and highlight some intriguing adaptations found in the Drosophila kinetochore. ..
  36. Moreno J, Miranda Azpiazu P, García Bea A, Younkin J, Cui M, Kozlenkov A, et al. Allosteric signaling through an mGlu2 and 5-HT2A heteromeric receptor complex and its potential contribution to schizophrenia. Sci Signal. 2016;9:ra5 pubmed publisher
    Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) can form multiprotein complexes (heteromers), which can alter the pharmacology and functions of the constituent receptors...
  37. Montavon T, Kwon Y, Zimmermann A, Hammann P, Vincent T, Cognat V, et al. A specific dsRNA-binding protein complex selectively sequesters endogenous inverted-repeat siRNA precursors and inhibits their processing. Nucleic Acids Res. 2017;45:1330-1344 pubmed publisher
    ..The existence of such a complex and its implication regarding the still elusive biological function of plant endoIR-siRNA will be discussed. ..
  38. Deng Y, Asbury C. Simultaneous Manipulation and Super-Resolution Fluorescence Imaging of Individual Kinetochores Coupled to Microtubule Tips. Methods Mol Biol. 2017;1486:437-467 pubmed publisher
    Kinetochores are large multiprotein complexes that drive mitotic chromosome movements by mechanically coupling them to the growing and shortening tips of spindle microtubules...
  39. Makowski M, Willems E, Jansen P, Vermeulen M. Cross-linking immunoprecipitation-MS (xIP-MS): Topological Analysis of Chromatin-associated Protein Complexes Using Single Affinity Purification. Mol Cell Proteomics. 2016;15:854-65 pubmed publisher
    ..This work, therefore, demonstrates that xIP-MS is a robust, flexible, and widely applicable methodology for interrogating chromatin-associated protein complex architectures. ..
  40. Chen Z, Morales J, Guerrero P, Sun H, McCarty J. PTPN12/PTP-PEST Regulates Phosphorylation-Dependent Ubiquitination and Stability of Focal Adhesion Substrates in Invasive Glioblastoma Cells. Cancer Res. 2018;78:3809-3822 pubmed publisher
    ..protein (Vcp), an ATP-dependent protein segregase that selectively extracts ubiquitinated proteins from multiprotein complexes and targets them for degradation via the ubiquitin proteasome system...
  41. Ye X, Zhou Q, Matsumoto Y, Moriyama M, Kageyama S, Komatsu M, et al. Inhibition of Glutaminolysis Inhibits Cell Growth via Down-regulating Mtorc1 Signaling in Lung Squamous Cell Carcinoma. Anticancer Res. 2016;36:6021-6029 pubmed
    ..Targeting glutaminolysis may represent a potential therapeutic strategy for the treatment of Gln-dependent lung squamous cell carcinomas. ..
  42. Tran L, Basdevant N, Prévost C, Ha Duong T. Structure of ring-shaped Aβ₄₂ oligomers determined by conformational selection. Sci Rep. 2016;6:21429 pubmed publisher
    ..In addition to high resolution models of these oligomers, this study provides support for the conformational selection mechanism of Aβ peptide self-assembly. ..
  43. Engel C, Gubbey T, Neyer S, Sainsbury S, Oberthuer C, Baejen C, et al. Structural Basis of RNA Polymerase I Transcription Initiation. Cell. 2017;169:120-131.e22 pubmed publisher
    ..Comparison with the Pol II system suggests that promoter specificity relies on a distinct "bendability" and "meltability" of the promoter sequence that enables contacts between initiation factors, DNA, and polymerase. ..
  44. Ding B, Zhong Q. Zinc deficiency: An unexpected trigger for autophagy. J Biol Chem. 2017;292:8531-8532 pubmed publisher
    ..A recent study shows that, in yeast, zinc depletion acts in a similar fashion. Depletion of this essential nutrient induces non-selective autophagy by inhibiting TORC1, leading to release and recycling of zinc from degraded proteins. ..
  45. Wang X, Proud C. mTORC2 is a tyrosine kinase. Cell Res. 2016;26:1-2 pubmed publisher
    ..In their recent study, Yin et al. show that mTOR can regulate signaling through the insulin-like growth factor 1 receptor and that it possesses a new enzymatic activity - the ability to phosphorylate proteins on tyrosine residues. ..
  46. Eiseler T, Wille C, Koehler C, Illing A, Seufferlein T. Protein Kinase D2 Assembles a Multiprotein Complex at the Trans-Golgi Network to Regulate Matrix Metalloproteinase Secretion. J Biol Chem. 2016;291:462-77 pubmed publisher
    ..In conclusion, our data indicate that PKD2 is a core factor in the formation of this multiprotein complex at the TGN that controls constitutive secretion of matrix metalloproteinase cargo. ..
  47. Drew K, Lee C, Huizar R, Tu F, Borgeson B, McWhite C, et al. Integration of over 9,000 mass spectrometry experiments builds a global map of human protein complexes. Mol Syst Biol. 2017;13:932 pubmed publisher
    ..MAP ( serves as a valuable resource for better understanding the core cellular functions of human proteins and helping to determine mechanistic foundations of human disease. ..
  48. Spiller M, Guo L, Wang Q, Tran P, Lu H. Mitochondrial Tim9 protects Tim10 from degradation by the protease Yme1. Biosci Rep. 2015;35: pubmed publisher
    ..We propose that Tim10, rather than the hexameric Tim9-Tim10 complex, is the functional form of these proteins. ..
  49. Buszewicz D, Archacki R, Palusiński A, Kotlinski M, Fogtman A, Iwanicka Nowicka R, et al. HD2C histone deacetylase and a SWI/SNF chromatin remodelling complex interact and both are involved in mediating the heat stress response in Arabidopsis. Plant Cell Environ. 2016;39:2108-22 pubmed publisher
    Studies in yeast and animals have revealed that histone deacetylases (HDACs) often act as components of multiprotein complexes, including chromatin remodelling complexes (CRCs)...
  50. Gordon J, Aibara S, Stewart M. Structure of the Sac3 RNA-binding M-region in the Saccharomyces cerevisiae TREX-2 complex. Nucleic Acids Res. 2017;45:5577-5585 pubmed publisher
  51. Wang J, Blevins T, Podicheti R, Haag J, Tan E, Wang F, et al. Mutation of Arabidopsis SMC4 identifies condensin as a corepressor of pericentromeric transposons and conditionally expressed genes. Genes Dev. 2017;31:1601-1614 pubmed publisher
    ..Collectively, our genome-wide analyses implicate condensin in the suppression of hundreds of loci, acting in both DNA methylation-dependent and methylation-independent pathways. ..
  52. Hasumi H, Baba M, Hasumi Y, Furuya M, Yao M. Birt-Hogg-Dubé syndrome: Clinical and molecular aspects of recently identified kidney cancer syndrome. Int J Urol. 2016;23:204-10 pubmed publisher
  53. Ramachandran S, Osterhaus S, Parekh K, Jacobi A, Behlke M, McCray P. SYVN1, NEDD8, and FBXO2 Proteins Regulate ?F508 Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Ubiquitin-mediated Proteasomal Degradation. J Biol Chem. 2016;291:25489-25504 pubmed
    ..It suggests that SYVN1 and FBXO2 represent two distinct multiprotein complexes that may degrade ?F508-CFTR in airway epithelia and identifies a new role for NEDD8 in regulating ?F508-..