SGTA interacts with the proteasomal ubiquitin receptor Rpn13 via a carboxylate clamp mechanism.
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.
Department of Chemistry, King's College London, Britannia House, Trinity Street, London, SE1 1DB, U.K.
Arjun
A
Thapaliya
School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, The Michael Smith Building, Oxford Road, Manchester, M13 9PT, U.K.
Yvonne
Y
Nyathi
Department of Chemistry, King's College London, Britannia House, Trinity Street, London, SE1 1DB, U.K.
Santiago
S
Martínez-Lumbreras
Department of Chemistry, King's College London, Britannia House, Trinity Street, London, SE1 1DB, U.K.
Ewelina M
EM
Krysztofinska
Department of Chemistry, King's College London, Britannia House, Trinity Street, London, SE1 1DB, U.K.
Nicola J
NJ
Evans
Department of Chemistry, King's College London, Britannia House, Trinity Street, London, SE1 1DB, U.K.
Isabelle L
IL
Terry
School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, The Michael Smith Building, Oxford Road, Manchester, M13 9PT, U.K.
Stephen
S
High
Department of Chemistry, King's College London, Britannia House, Trinity Street, London, SE1 1DB, U.K.
Rivka L
RL
Isaacson
D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones; D011485:Protein Binding; D000072417:Protein Domains
C500781:ADRM1 protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; C114575:SGTA protein, human