5IRS

crystal structure of the proteasomal Rpn13 PRU-domain

Summary for 5IRS

• Entry DOI: 10.2210/pdb5irs/pdb
• Descriptor: Proteasomal ubiquitin receptor ADRM1, 2,3-DIHYDROXY-1,4-DITHIOBUTANE (3 entities in total)
• Functional Keywords: ubiquitin, protein binding
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: Q16186
• Total number of polymer chains: 1
• Total formula weight: 16919.35

Authors

Chen, X.,Shi, K.,Walters, K.,Aihara, H. (deposition date: 2016-03-14, release date: 2016-07-20, Last modification date: 2024-10-16)

Primary citation

Chen, X.,Randles, L.,Shi, K.,Tarasov, S.G.,Aihara, H.,Walters, K.J.
Structures of Rpn1 T1:Rad23 and hRpn13:hPLIC2 Reveal Distinct Binding Mechanisms between Substrate Receptors and Shuttle Factors of the Proteasome.
Structure, 24:1257-1270, 2016

PubMed Abstract: Three receptors (Rpn1/S2/PSMD2, Rpn10/S5a, Rpn13/Adrm1) in the proteasome bind substrates by interacting with conjugated ubiquitin chains and/or shuttle factors (Rad23/HR23, Dsk2/PLIC/ubiquilin, Ddi1) that carry ubiquitinated substrates to proteasomes. We solved the structure of two such receptors with their preferred shuttle factor, namely hRpn13(Pru):hPLIC2(UBL) and scRpn1 T1:scRad23(UBL). We find that ubiquitin folds in Rad23 and Dsk2 are fine-tuned by residue substitutions to achieve high affinity for Rpn1 and Rpn13, respectively. A single substitution in hPLIC2 yields enhanced interactions with the Rpn13 ubiquitin contact surface and sterically blocks hRpn13 binding to its preferred ubiquitin chain type, K48-linked chains. Rpn1 T1 binds two ubiquitins in tandem and we find that Rad23 binds exclusively to the higher-affinity Helix28/Helix30 site. Rad23 contacts at Helix28/Helix30 are optimized compared to ubiquitin by multiple conservative amino acid substitutions. Thus, shuttle factors deliver substrates to proteasomes through fine-tuned ubiquitin-like surfaces.

PubMed: 27396824
DOI: 10.1016/j.str.2016.05.018

Experimental method

X-RAY DIFFRACTION (1.796 Å)