David Komander

Summary

Affiliation: University of Cambridge
Country: UK

Publications

  1. pmc Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains
    David Komander
    Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    EMBO Rep 10:466-73. 2009
  2. doi request reprint Two-sided ubiquitin binding explains specificity of the TAB2 NZF domain
    Yogesh Kulathu
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Nat Struct Mol Biol 16:1328-30. 2009
  3. doi request reprint The ubiquitin code
    David Komander
    Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge, CB2 0QH, United Kingdom
    Annu Rev Biochem 81:203-29. 2012
  4. doi request reprint Breaking the chains: structure and function of the deubiquitinases
    David Komander
    Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK
    Nat Rev Mol Cell Biol 10:550-63. 2009
  5. doi request reprint Mechanism, specificity and structure of the deubiquitinases
    David Komander
    Protein and Nucleic Acid Chemistry Division, Research Council Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK
    Subcell Biochem 54:69-87. 2010
  6. doi request reprint The emerging complexity of protein ubiquitination
    David Komander
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK
    Biochem Soc Trans 37:937-53. 2009
  7. doi request reprint CYLD tidies up dishevelled signaling
    David Komander
    Medical Research Council Laboratory of Molecular Biology, Protein and Nucleic Acid Chemistry Division, Hills Road, Cambridge CB2 0QH, UK
    Mol Cell 37:589-90. 2010
  8. pmc Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne
    Anja Bremm
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Nat Struct Mol Biol 17:939-47. 2010
  9. doi request reprint An ankyrin-repeat ubiquitin-binding domain determines TRABID's specificity for atypical ubiquitin chains
    Julien D F Licchesi
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Nat Struct Mol Biol 19:62-71. 2012
  10. doi request reprint Polyubiquitin binding and cross-reactivity in the USP domain deubiquitinase USP21
    Yu Ye
    Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    EMBO Rep 12:350-7. 2011

Collaborators

  • Jason W Chin
  • Kay Hofmann
  • Huib Ovaa
  • Felix Randow
  • David Barford
  • Keith D Wilkinson
  • David Klenerman
  • Angel Orte
  • Michael Rape
  • Nia J Bryant
  • Mariann Bienz
  • Sylvie Urbé
  • Michael J Clague
  • Hartmut Scheel
  • Yogesh Kulathu
  • Masato Akutsu
  • Yu Ye
  • Anja Bremm
  • Stefan M V Freund
  • Tobias Wauer
  • Tycho E T Mevissen
  • Natalia von Muhlinen
  • Satpal Virdee
  • Manuela K Hospenthal
  • Trevor J Rutherford
  • Kirstin Keusekotten
  • Nadia Arnaudo
  • Farid El Oualid
  • Benjamin J Ravenhill
  • Stuart Bloor
  • Agnes Foeglein
  • Julien D F Licchesi
  • Ceri M Wiggins
  • Paul P Geurink
  • Reggy Ekkebus
  • Paul R Elliott
  • Francisco J Garcia
  • Berthe Katrine Fiil
  • Martin Busch
  • Rune Busk Damgaard
  • Manuela Kathrin Hospenthal
  • Mads Gyrd-Hansen
  • Kate S Carroll
  • Laura Glockner
  • Paul Ronald Elliott
  • Daniel Krappmann
  • Georg Blaser
  • Shehu Ibrahim
  • Mathew H Horrocks
  • Sophie E Jackson
  • Juliusz Mieszczanek
  • Maria J Ruedas-Rama
  • Alexander A Zhukov
  • Francisca Reyes-Turcu
  • Mark Johnson
  • Christopher A Lamb
  • Radoslav I Enchev
  • Simon J Cook
  • Claire L Joyce
  • Yosef Shaul
  • Peter Tsvetkov
  • Duy P Nguyen

Detail Information

Publications25

  1. pmc Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains
    David Komander
    Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    EMBO Rep 10:466-73. 2009
    ..Our results highlight remarkable specificity determinants within the ubiquitin system...
  2. doi request reprint Two-sided ubiquitin binding explains specificity of the TAB2 NZF domain
    Yogesh Kulathu
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Nat Struct Mol Biol 16:1328-30. 2009
    ..The conformational constraints imposed by TAB2 on a Lys63 dimer cannot be adopted by linear chains, explaining why TAK1 cannot be activated by linear ubiquitination events...
  3. doi request reprint The ubiquitin code
    David Komander
    Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge, CB2 0QH, United Kingdom
    Annu Rev Biochem 81:203-29. 2012
    ..Reminiscent of a code, the various ubiquitin modifications adopt distinct conformations and lead to different outcomes in cells. Here, we discuss the structure, assembly, and function of this ubiquitin code...
  4. doi request reprint Breaking the chains: structure and function of the deubiquitinases
    David Komander
    Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK
    Nat Rev Mol Cell Biol 10:550-63. 2009
    ..Due to their wide-ranging involvement in key regulatory processes, these enzymes might provide new therapeutic targets...
  5. doi request reprint Mechanism, specificity and structure of the deubiquitinases
    David Komander
    Protein and Nucleic Acid Chemistry Division, Research Council Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK
    Subcell Biochem 54:69-87. 2010
    ..The individual deubiquitinase families are discussed with a focus on structure, regulation and specificity features for selected enzymes...
  6. doi request reprint The emerging complexity of protein ubiquitination
    David Komander
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK
    Biochem Soc Trans 37:937-53. 2009
    ..For example, ubiquitination may have important allosteric roles in protein regulation that are currently not appreciated...
  7. doi request reprint CYLD tidies up dishevelled signaling
    David Komander
    Medical Research Council Laboratory of Molecular Biology, Protein and Nucleic Acid Chemistry Division, Hills Road, Cambridge CB2 0QH, UK
    Mol Cell 37:589-90. 2010
    ..In this issue of Molecular Cell, Maurice and colleagues demonstrate that nondegradative Lys63-linked polyubiquitin chains modulate Dishevelled (Dvl) activity upstream in the Wnt/beta-catenin signaling pathway...
  8. pmc Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne
    Anja Bremm
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Nat Struct Mol Biol 17:939-47. 2010
    ..Our data highlight the intrinsic specificity of the ubiquitin system that extends to Lys11-linked chains and emphasize that differentially linked polyubiquitin chains must be regarded as independent post-translational modifications...
  9. doi request reprint An ankyrin-repeat ubiquitin-binding domain determines TRABID's specificity for atypical ubiquitin chains
    Julien D F Licchesi
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Nat Struct Mol Biol 19:62-71. 2012
    ..Our data are consistent with AnkUBD functioning as an enzymatic S1' ubiquitin-binding site, which orients a ubiquitin chain so that Lys29 and Lys33 linkages are cleaved preferentially...
  10. doi request reprint Polyubiquitin binding and cross-reactivity in the USP domain deubiquitinase USP21
    Yu Ye
    Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    EMBO Rep 12:350-7. 2011
    ..We also rationalize the inability of USP21 to target NEDD8 and identify differences that allow USPs to distinguish between structurally related modifications...
  11. pmc An essential role for the ATG8 ortholog LC3C in antibacterial autophagy
    Natalia von Muhlinen
    MRC Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Cambridge, UK
    Autophagy 9:784-6. 2013
    ..Our findings provide a new layer of regulation to selective autophagy, suggesting that specific interactions between autophagy receptors and the ATG8 orthologs are of biological importance...
  12. doi request reprint Regulation of A20 and other OTU deubiquitinases by reversible oxidation
    Yogesh Kulathu
    Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK
    Nat Commun 4:1569. 2013
    ..Using chemical tools to detect sulphenic acid intermediates, we show that many ovarian tumour deubiquitinases undergo reversible oxidation upon treatment with HO, revealing a new mechanism to regulate deubiquitinase activity...
  13. pmc Molecular basis for ubiquitin and ISG15 cross-reactivity in viral ovarian tumor domains
    Masato Akutsu
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, United Kingdom
    Proc Natl Acad Sci U S A 108:2228-33. 2011
    ..ISGylation in viral infection. Furthermore, the crystal structures will allow structure-based design of antiviral agents targeting this enzyme...
  14. pmc OTU Deubiquitinases Reveal Mechanisms of Linkage Specificity and Enable Ubiquitin Chain Restriction Analysis
    Tycho E T Mevissen
    Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK Freie Universität Berlin, Fachbereich Biologie, Chemie, Pharmazie, D 14195 Berlin, Germany
    Cell 154:169-84. 2013
    ..We introduce Ub chain restriction analysis, in which OTU DUBs are used as restriction enzymes to reveal linkage type and the relative abundance of Ub chains on substrates. ..
  15. pmc LC3C, bound selectively by a noncanonical LIR motif in NDP52, is required for antibacterial autophagy
    Natalia von Muhlinen
    MRC Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Cambridge CB2 0QH, UK
    Mol Cell 48:329-42. 2012
    ..Our report illustrates that specificity in the interaction between autophagy receptors and autophagy machinery is of functional importance to execute selective autophagy...
  16. doi request reprint Atypical ubiquitylation - the unexplored world of polyubiquitin beyond Lys48 and Lys63 linkages
    Yogesh Kulathu
    Medical Research Council MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK
    Nat Rev Mol Cell Biol 13:508-23. 2012
    ..The importance of Lys11 linkages and Met1 linkages in cell cycle regulation and nuclear factor-κB activation, respectively, highlight that the different ubiquitin chain types should be considered as functionally independent PTMs...
  17. doi request reprint Emerging roles for Lys11-linked polyubiquitin in cellular regulation
    Anja Bremm
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK
    Trends Biochem Sci 36:355-63. 2011
    ..Notably, mechanistic insights have revealed how the E2 ubiquitin-conjugating enzyme UBE2S achieves its Lys11 linkage specificity, and two structures of Lys11-linked polyubiquitin highlight the dynamic nature of this compact chain type...
  18. pmc OTULIN Antagonizes LUBAC Signaling by Specifically Hydrolyzing Met1-Linked Polyubiquitin
    Kirstin Keusekotten
    Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK
    Cell 153:1312-26. 2013
    ..We show that OTULIN binds LUBAC and that overexpression of OTULIN prevents TNFα-induced NEMO association with ubiquitinated RIPK1. Our data suggest that OTULIN regulates Met1-polyUb signaling...
  19. doi request reprint Assembly, analysis and architecture of atypical ubiquitin chains
    Manuela K Hospenthal
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Nat Struct Mol Biol 20:555-65. 2013
    ..Interactions via the Ile36 patch can displace Leu8 from the Ile44 patch, leading to marked structural perturbations of Ub...
  20. pmc Ubiquitin chain conformation regulates recognition and activity of interacting proteins
    Yu Ye
    Division of Protein and Nucleic Acids Chemistry, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK
    Nature 492:266-70. 2012
    ....
  21. doi request reprint Synthesis and analysis of K11-linked ubiquitin chains
    Anja Bremm
    Protein and Nucleic Acid Chemistry Division, MRC Laboratory of Molecular Biology, Cambridge, UK
    Methods Mol Biol 832:219-28. 2012
    ..Here, we describe a method to synthesise K11-linked ubiquitin chains in vitro by exploiting the intrinsic K11-specificity of the E2 enzyme UBE2S...
  22. doi request reprint Engineered diubiquitin synthesis reveals Lys29-isopeptide specificity of an OTU deubiquitinase
    Satpal Virdee
    Medical Research Council Laboratory of Molecular Biology, Cambridge, England, United Kingdom
    Nat Chem Biol 6:750-7. 2010
    ..Moreover, we profile a panel containing 10% of the known human deubiquitinases on Lys6- and Lys29-linked ubiquitin and discover that TRABID cleaves the Lys29 linkage 40-fold more efficiently than the Lys63 linkage...
  23. doi request reprint BIM(EL), an intrinsically disordered protein, is degraded by 20S proteasomes in the absence of poly-ubiquitylation
    Ceri M Wiggins
    Laboratory of Molecular Signalling, The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK
    J Cell Sci 124:969-77. 2011
    ..These results provide new insights into the regulation of BIM(EL) by defining a novel ubiquitin-independent pathway for the proteasome-dependent destruction of this highly toxic protein...
  24. pmc Structure of the human Parkin ligase domain in an autoinhibited state
    Tobias Wauer
    Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    EMBO J 32:2099-112. 2013
    ..Opening of intra-domain interfaces activates Parkin, and enables Ub-based suicide probes to modify Cys431. The structure further reveals a putative phospho-peptide docking site in the UPD, and explains many PD-causing mutations. ..
  25. doi request reprint Dissection of USP catalytic domains reveals five common insertion points
    Yu Ye
    MRC Laboratory of Molecular Biology, Protein and Nucleic Acid Chemistry Division, Hills Road, Cambridge, UK
    Mol Biosyst 5:1797-808. 2009
    ..Yeast USP domains have a different pattern of inserted sequences, suggesting that the insertions are hotspots for evolutionary diversity to expand USP functionality...