A single MIU motif of MINDY-1 recognizes K48-linked polyubiquitin chains

Yosua Kristariyanto, Syed Arif Abdul Rehman, Simone Weidlich, Axel Knebel, Yogesh Kulathu (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

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The eight different types of ubiquitin (Ub) chains that can be formed play important roles in diverse cellular processes. Linkage-selective recognition of Ub chains by Ub-binding domain (UBD)-containing proteins is central to coupling different Ub signals to specific cellular responses. The motif interacting with ubiquitin (MIU) is a small UBD that has been characterized for its binding to monoUb. The recently discovered deubiquitinase MINDY-1/FAM63A contains a tandem MIU repeat (tMIU) that is highly selective at binding to K48-linked polyUb. We here identify that this linkage-selective binding is mediated by a single MIU motif (MIU2) in MINDY-1. The crystal structure of MIU2 in complex with K48 linked polyubiquitin chains reveals that MIU2 on its own binds to all three Ub moieties in an open conformation that can only be accommodated by K48-linked triUb. The weak Ub binder MIU1 increases overall affinity of the tMIU for polyUb chains without affecting its linkage selectivity. Our analyses reveal new concepts for linkage selectivity and polyUb recognition by UBDs.
Original languageEnglish
Article numbere201643205
Pages (from-to)392-402
Number of pages11
JournalEMBO Reports
Issue number3
Early online date12 Jan 2017
Publication statusPublished - 1 Mar 2017


  • MINDY deubiquitinase
  • motif interacting with ubiquitin
  • polyubiquitin
  • ubiquitin binding domain
  • ubiquitin signaling


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