PDBsum entry 2nbv

Protein binding

PDB id: 2nbv

Contents

Protein chains

110 a.a.

78 a.a.

PDB id:

2nbv

Name:

Protein binding

Title:

Solution structure of the rpn13 pru domain engaging the hplic2 ubl domain

Structure:

Proteasomal ubiquitin receptor adrm1. Chain: a. Fragment: residues 1-150. Synonym: 110 kda cell membrane glycoprotein, gp110, adhesion- regulating molecule 1, arm-1, proteasome regulatory particle non- atpase 13, hrpn13, rpn13 homolog. Engineered: yes. Ubiquilin-2. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: adrm1, gp110. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: ubqln2, n4bp4, plic2, hrihfb2157.

NMR struc:

20 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:

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

Protein chain

Q16186  (ADRM1_HUMAN) -  Proteasomal ubiquitin receptor ADRM1 from Homo sapiens

Seq: 407 a.a.

Struc: 110 a.a.

Protein chain

Q9UHD9  (UBQL2_HUMAN) -  Ubiquilin-2 from Homo sapiens

Seq: 624 a.a.

Struc: 78 a.a.

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.