K29-selective ubiquitin binding domain reveals structural basis of specificity and heterotypic nature of K29 polyubiquitin

Yosua Adi Kristariyanto, Syed Arif Abdul Rehman, David G. Campbell, Nicholas A. Morrice, Clare Johnson, Rachel Toth, Yogesh Kulathu

    Research output: Contribution to journalArticle

    61 Citations (Scopus)
    63 Downloads (Pure)

    Abstract

    Polyubiquitin chains regulate diverse cellular processes through the ability of ubiquitin to form chains of eight different linkage types. Although detected in yeast and mammals, little is known about K29-linked polyubiquitin. Here we report the generation of K29 chains in vitro using a ubiquitin chain-editing complex consisting of the HECT E3 ligase UBE3C and the deubiquitinase vOTU. We determined the crystal structure of K29-linked diubiquitin, which adopts an extended conformation with the hydrophobic patches on both ubiquitin moieties exposed and available for binding. Indeed, the crystal structure of the NZF1 domain of TRABID in complex with K29 chains reveals a binding mode that involves the hydrophobic patch on only one of the ubiquitin moieties and exploits the flexibility of K29 chains to achieve linkage selective binding. Further, we establish methods to study K29-linked polyubiquitin and find that K29 linkages exist in cells within mixed or branched chains containing other linkages.

    Original languageEnglish
    Pages (from-to)83-94
    Number of pages12
    JournalMolecular Cell
    Volume58
    Issue number1
    Early online date5 Mar 2015
    DOIs
    Publication statusPublished - 2 Apr 2015

    Fingerprint

    Polyubiquitin
    Ubiquitin
    Ubiquitin-Protein Ligases
    Mammals
    Yeasts

    Cite this

    @article{b320222646ba4740aafbb558d677a22b,
    title = "K29-selective ubiquitin binding domain reveals structural basis of specificity and heterotypic nature of K29 polyubiquitin",
    abstract = "Polyubiquitin chains regulate diverse cellular processes through the ability of ubiquitin to form chains of eight different linkage types. Although detected in yeast and mammals, little is known about K29-linked polyubiquitin. Here we report the generation of K29 chains in vitro using a ubiquitin chain-editing complex consisting of the HECT E3 ligase UBE3C and the deubiquitinase vOTU. We determined the crystal structure of K29-linked diubiquitin, which adopts an extended conformation with the hydrophobic patches on both ubiquitin moieties exposed and available for binding. Indeed, the crystal structure of the NZF1 domain of TRABID in complex with K29 chains reveals a binding mode that involves the hydrophobic patch on only one of the ubiquitin moieties and exploits the flexibility of K29 chains to achieve linkage selective binding. Further, we establish methods to study K29-linked polyubiquitin and find that K29 linkages exist in cells within mixed or branched chains containing other linkages.",
    author = "Kristariyanto, {Yosua Adi} and {Abdul Rehman}, {Syed Arif} and Campbell, {David G.} and Morrice, {Nicholas A.} and Clare Johnson and Rachel Toth and Yogesh Kulathu",
    note = "This work was supported by the Medical Research Council UK, Wellcome Trust (grant number 094090) and the pharmaceutical companies supporting the Division of Signal Transduction Therapy (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck KGaA, Janssen Pharmaceutica, and Pfizer).",
    year = "2015",
    month = "4",
    day = "2",
    doi = "10.1016/j.molcel.2015.01.041",
    language = "English",
    volume = "58",
    pages = "83--94",
    journal = "Molecular Cell",
    issn = "1097-2765",
    publisher = "Elsevier",
    number = "1",

    }

    K29-selective ubiquitin binding domain reveals structural basis of specificity and heterotypic nature of K29 polyubiquitin. / Kristariyanto, Yosua Adi; Abdul Rehman, Syed Arif; Campbell, David G.; Morrice, Nicholas A.; Johnson, Clare; Toth, Rachel; Kulathu, Yogesh.

    In: Molecular Cell, Vol. 58, No. 1, 02.04.2015, p. 83-94.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - K29-selective ubiquitin binding domain reveals structural basis of specificity and heterotypic nature of K29 polyubiquitin

    AU - Kristariyanto, Yosua Adi

    AU - Abdul Rehman, Syed Arif

    AU - Campbell, David G.

    AU - Morrice, Nicholas A.

    AU - Johnson, Clare

    AU - Toth, Rachel

    AU - Kulathu, Yogesh

    N1 - This work was supported by the Medical Research Council UK, Wellcome Trust (grant number 094090) and the pharmaceutical companies supporting the Division of Signal Transduction Therapy (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck KGaA, Janssen Pharmaceutica, and Pfizer).

    PY - 2015/4/2

    Y1 - 2015/4/2

    N2 - Polyubiquitin chains regulate diverse cellular processes through the ability of ubiquitin to form chains of eight different linkage types. Although detected in yeast and mammals, little is known about K29-linked polyubiquitin. Here we report the generation of K29 chains in vitro using a ubiquitin chain-editing complex consisting of the HECT E3 ligase UBE3C and the deubiquitinase vOTU. We determined the crystal structure of K29-linked diubiquitin, which adopts an extended conformation with the hydrophobic patches on both ubiquitin moieties exposed and available for binding. Indeed, the crystal structure of the NZF1 domain of TRABID in complex with K29 chains reveals a binding mode that involves the hydrophobic patch on only one of the ubiquitin moieties and exploits the flexibility of K29 chains to achieve linkage selective binding. Further, we establish methods to study K29-linked polyubiquitin and find that K29 linkages exist in cells within mixed or branched chains containing other linkages.

    AB - Polyubiquitin chains regulate diverse cellular processes through the ability of ubiquitin to form chains of eight different linkage types. Although detected in yeast and mammals, little is known about K29-linked polyubiquitin. Here we report the generation of K29 chains in vitro using a ubiquitin chain-editing complex consisting of the HECT E3 ligase UBE3C and the deubiquitinase vOTU. We determined the crystal structure of K29-linked diubiquitin, which adopts an extended conformation with the hydrophobic patches on both ubiquitin moieties exposed and available for binding. Indeed, the crystal structure of the NZF1 domain of TRABID in complex with K29 chains reveals a binding mode that involves the hydrophobic patch on only one of the ubiquitin moieties and exploits the flexibility of K29 chains to achieve linkage selective binding. Further, we establish methods to study K29-linked polyubiquitin and find that K29 linkages exist in cells within mixed or branched chains containing other linkages.

    U2 - 10.1016/j.molcel.2015.01.041

    DO - 10.1016/j.molcel.2015.01.041

    M3 - Article

    VL - 58

    SP - 83

    EP - 94

    JO - Molecular Cell

    JF - Molecular Cell

    SN - 1097-2765

    IS - 1

    ER -