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FEBS J. 2016 Feb;283(4):662-77. doi: 10.1111/febs.13618. Epub 2015 Dec 31.

A conserved island of BAG6/Scythe is related to ubiquitin domains and participates in short hydrophobicity recognition.

Author information

1
Department of Biological Sciences, Tokyo Metropolitan University, Japan.
2
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
3
Picobiology Institute, Graduate School of Life Science, University of Hyogo, Japan.
4
Structural Biology Research Center, Photon Factory, IMSS, High Energy Accelerator Research Organization (KEK), Tsukuba, Japan.

Abstract

BAG6 (also called Scythe) interacts with the exposed hydrophobic regions of newly synthesized proteins and escorts them to the degradation machinery through mechanisms that remain to be elucidated. In this study, we provide evidence that BAG6 physically interacts with the model defective protein substrate CL1 in a manner that depends directly on its short hydrophobicity. We found that the N terminus of BAG6 contains an evolutionarily conserved island tentatively designated the BAG6 ubiquitin-linked domain. Partial deletion of this domain in the BAG6 N-terminal fragment abolished in cell recognition of polyubiquitinated polypeptides as well as the hydrophobicity-mediated recognition of the CL1 degron in cell and in vitro. These observations suggest a mechanism whereby the BAG6 ubiquitin-linked domain provides a platform for discriminating substrates with shorter hydrophobicity stretches as a signal for defective proteins.

KEYWORDS:

26S proteasome; BAT3; CL1 degron; protein quality control; ubiquitin

PMID:
26663859
DOI:
10.1111/febs.13618
[Indexed for MEDLINE]
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