PDBsum entry 6i4x

Signaling protein

PDB id: 6i4x

Contents

Protein chains

103 a.a.

86 a.a.

158 a.a.

Ligands

SER-PHE-GLU-PTR-THR-ILE-LEU-ASP-PRO

PEG

Waters ×11

PDB id:

6i4x

Name:

Signaling protein

Title:

Crystal structure of socs2:elongin c:elongin b in complex with erythropoietin receptor peptide

Structure:

Elongin-b. Chain: b. Synonym: elob,elongin 18 kda subunit,RNA polymerase ii transcription factor siii subunit b,siii p18,transcription elongation factor b polypeptide 2. Engineered: yes. Elongin-c. Chain: c. Synonym: eloc,elongin 15 kda subunit,RNA polymerase ii transcription

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: elob, tceb2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: eloc, tceb1. Gene: socs2, cis2, ssi2, stati2. Synthetic: yes.

Resolution:

2.69Å R-factor: 0.199 R-free: 0.235

Authors:

W.W.Kung,S.Ramachandran,N.Makukhin,E.Bruno,A.Ciulli

Key ref:

W.W.Kung et al. (2019). Structural insights into substrate recognition by the SOCS2 E3 ubiquitin ligase. Nat Commun, 10, 2534. PubMed id: 31182716 DOI: 10.1038/s41467-019-10190-4

Date:

12-Nov-18 Release date: 29-May-19

Protein chain

Q15370  (ELOB_HUMAN) -  Elongin-B from Homo sapiens

Seq: 118 a.a.

Struc: 103 a.a.*

Protein chain

Q15369  (ELOC_HUMAN) -  Elongin-C from Homo sapiens

Seq: 112 a.a.

Struc: 86 a.a.

Protein chain

O14508  (SOCS2_HUMAN) -  Suppressor of cytokine signaling 2 from Homo sapiens

Seq: 198 a.a.

Struc: 158 a.a.*

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

DOI no: 10.1038/s41467-019-10190-4

Nat Commun 10:2534 (2019)

PubMed id: 31182716

Structural insights into substrate recognition by the SOCS2 E3 ubiquitin ligase.

W.W.Kung, S.Ramachandran, N.Makukhin, E.Bruno, A.Ciulli.

ABSTRACT

The suppressor of cytokine signaling 2 (SOCS2) acts as substrate recognition subunit of a Cullin5 E3 ubiquitin ligase complex. SOCS2 binds to phosphotyrosine-modified epitopes as degrons for ubiquitination and proteasomal degradation, yet the molecular basis of substrate recognition has remained elusive. Here, we report co-crystal structures of SOCS2-ElonginB-ElonginC in complex with phosphorylated peptides from substrates growth hormone receptor (GHR-pY595) and erythropoietin receptor (EpoR-pY426) at 1.98 Å and 2.69 Å, respectively. Both peptides bind in an extended conformation recapitulating the canonical SH2 domain-pY pose, but capture different conformations of the EF loop via specific hydrophobic interactions. The flexible BG loop is fully defined in the electron density, and does not contact the substrate degron directly. Cancer-associated SNPs located around the pY pocket weaken substrate-binding affinity in biophysical assays. Our findings reveal insights into substrate recognition and specificity by SOCS2, and provide a blueprint for small molecule ligand design.