Mechanistic Insights into Recognitions of Ubiquitin and Myosin VI by Autophagy Receptor TAX1BP1

J Mol Biol. 2018 Sep 14;430(18 Pt B):3283-3296. doi: 10.1016/j.jmb.2018.06.030. Epub 2018 Jun 27.

Abstract

TAX1BP1, a ubiquitin-binding adaptor, plays critical roles in the innate immunity and selective autophagy. During autophagy, TAX1BP1 may not only function as an autophagy receptor to recruit ubiquitylated substrates for autophagic degradation, but also serve as a Myosin VI cargo adaptor protein for mediating the maturation of autophagosome. However, the mechanistic basis underlying the specific interactions of TAX1BP1 with ubiquitin and Myosin VI remains elusive. Here, using biochemical, NMR and structural analyses, we elucidate the detailed binding mechanism and uncover the key determinants for the interaction between TAX1BP1 and ubiquitin. In addition, we reveal that both tandem zinc-fingers of TAX1BP1 and the conformational rigidity between them are required for the Myosin VI binding of TAX1BP1, and ubiquitin and Myosin VI are mutually exclusive in binding to TAX1BP1. Collectively, our findings provide mechanistic insights into the dual functions of TAX1BP1 in selective autophagy.

Keywords: Myosin VI; TAX1BP1; autophagy receptor; selective autophagy; ubiquitin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy*
  • Cell Line
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Models, Molecular
  • Myosin Heavy Chains / chemistry*
  • Myosin Heavy Chains / metabolism
  • Neoplasm Proteins / chemistry*
  • Neoplasm Proteins / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Structure-Activity Relationship
  • Ubiquitin / chemistry*
  • Ubiquitin / metabolism

Substances

  • Intracellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • TAX1BP1 protein, human
  • Ubiquitin
  • myosin VI
  • Myosin Heavy Chains