Structural and functional insights into the E3 ligase, RNF126

Ewelina M. Krysztofinska; Santiago Martínez-Lumbreras; Arjun Thapaliya; Nicola J. Evans; Stephen High; Rivka L. Isaacson

doi:10.1038/srep26433

Structural and functional insights into the E3 ligase, RNF126

Ewelina M. Krysztofinska, Santiago Martínez-Lumbreras, Arjun Thapaliya, Nicola J. Evans, Stephen High, Rivka L. Isaacson^*

^*Corresponding author for this work

Division of Molecular & Cellular Function (L5)

King's College London

Research output: Contribution to journal › Article › peer-review

Abstract

RNF126 is an E3 ubiquitin ligase that collaborates with the BAG6 sortase complex to ubiquitinate hydrophobic substrates in the cytoplasm that are destined for proteasomal recycling. Composed of a trimeric complex of BAG6, TRC35 and UBL4A the BAG6 sortase is also associated with SGTA, a co-chaperone from which it can obtain hydrophobic substrates. Here we solve the solution structure of the RNF126 zinc finger domain in complex with the BAG6 UBL domain. We also characterise an interaction between RNF126 and UBL4A and analyse the competition between SGTA and RNF126 for the N-terminal BAG6 binding site. This work sheds light on the sorting mechanism of the BAG6 complex and its accessory proteins which, together, decide the fate of stray hydrophobic proteins in the aqueous cytoplasm.

Original language	English
Article number	26433
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep26433
Publication status	Published - 19 May 2016

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10.1038/srep26433Licence: CC BY

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abstract = "RNF126 is an E3 ubiquitin ligase that collaborates with the BAG6 sortase complex to ubiquitinate hydrophobic substrates in the cytoplasm that are destined for proteasomal recycling. Composed of a trimeric complex of BAG6, TRC35 and UBL4A the BAG6 sortase is also associated with SGTA, a co-chaperone from which it can obtain hydrophobic substrates. Here we solve the solution structure of the RNF126 zinc finger domain in complex with the BAG6 UBL domain. We also characterise an interaction between RNF126 and UBL4A and analyse the competition between SGTA and RNF126 for the N-terminal BAG6 binding site. This work sheds light on the sorting mechanism of the BAG6 complex and its accessory proteins which, together, decide the fate of stray hydrophobic proteins in the aqueous cytoplasm.",

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AU - Krysztofinska, Ewelina M.

AU - Martínez-Lumbreras, Santiago

AU - Thapaliya, Arjun

AU - Evans, Nicola J.

AU - High, Stephen

AU - Isaacson, Rivka L.

PY - 2016/5/19

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Structural and functional insights into the E3 ligase, RNF126

Abstract

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