SGTA interacts with the proteasomal ubiquitin receptor Rpn13 via a carboxylate clamp mechanism

Arjun Thapaliya, Yvonne Nyathi, Santiago Martínez-Lumbreras, Ewelina M. Krysztofinska, Nicola J. Evans, Isabelle L. Terry, Stephen High, Rivka L. Isaacson

Research output: Contribution to journalArticlepeer-review

Abstract

The fate of secretory and membrane proteins that mislocalize to the cytosol is decided by a collaboration between cochaperone SGTA (small, glutamine-rich, tetratricopeptide repeat protein alpha) and the BAG6 complex, whose operation relies on multiple transient and subtly discriminated interactions with diverse binding partners. These include chaperones, membrane-targeting proteins and ubiquitination enzymes. Recently a direct interaction was discovered between SGTA and the proteasome, mediated by the intrinsic proteasomal ubiquitin receptor Rpn13. Here, we structurally and biophysically characterize this binding and identify a region of the Rpn13 C-terminal domain that is necessary and sufficient to facilitate it. We show that the contact occurs through a carboxylate clamp-mediated molecular recognition event with the TPR domain of SGTA, and provide evidence that the interaction can mediate the association of Rpn13 and SGTA in a cellular context.

Original languageEnglish
Article number36622
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 9 Nov 2016

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