PDBsum entry 2nbw

Protein binding

PDB id: 2nbw

Contents

Protein chains

131 a.a.

78 a.a.

PDB id:

2nbw

Name:

Protein binding

Title:

Solution structure of the rpn1 t1 site with the rad23 ubl domain

Structure:

26s proteasome regulatory subunit rpn1. Chain: a. Fragment: residues 482-612. Synonym: hmg-coa reductase degradation protein 2, proteasome non- atpase subunit 1. Engineered: yes. Uv excision repair protein rad23. Chain: b. Fragment: residues 1-78.

Source:

Saccharomyces cerevisiae s288c. Baker's yeast. Organism_taxid: 559292. Strain: atcc 204508 / s288c. Gene: rpn1, hrd2, nas1, rpd1, yhr027c. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: rad23, yel037c, sygp-orf29.

NMR struc:

10 models

Authors:

X.Chen,K.J.Walters

Key ref:

X.Chen et al. (2016). 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. PubMed id: 27396824 DOI: 10.1016/j.str.2016.05.018

Date:

14-Mar-16 Release date: 20-Jul-16

Protein chain

P38764  (RPN1_YEAST) -  26S proteasome regulatory subunit RPN1 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 993 a.a.

Struc: 131 a.a.

Protein chain

P32628  (RAD23_YEAST) -  UV excision repair protein RAD23 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 398 a.a.

Struc: 78 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

DOI no: 10.1016/j.str.2016.05.018

Structure 24:1257-1270 (2016)

PubMed id: 27396824

Structures of Rpn1 T1:Rad23 and hRpn13:hPLIC2 Reveal Distinct Binding Mechanisms between Substrate Receptors and Shuttle Factors of the Proteasome.

X.Chen, L.Randles, K.Shi, S.G.Tarasov, H.Aihara, K.J.Walters.

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.