PDBsum entry: 2c9w

Transcription regulation

PDB id: 2c9w

Contents

Protein chains

153 a.a. *

103 a.a. *

80 a.a. *

Ligands

SO4 ×3

Metals

_NI ×3

Waters ×172

* Residue conservation analysis

PDB id:

2c9w

Name:

Transcription regulation

Title:

Crystal structure of socs-2 in complex with elongin-b and elongin-c at 1.9a resolution

Structure:

Suppressor of cytokine signaling 2. Chain: a. Synonym: human socs2, socs-2, cytokine-inducible sh2 protei cis-2, stat-induced stat inhibitor 2, ssi-2. Engineered: yes. Transcription elongation factor b polypeptide 2. Chain: b. Synonym: human elongin b, RNA polymerase ii transcription f siii subunit b, siii p18, elongin b, elob, elongin 18 kda

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_cell_line: bl21(de3)-r3. Expression_system_taxid: 562

Biol. unit:

Trimer (from PDB file)

Resolution:

1.90Å R-factor: 0.187 R-free: 0.225

Authors:

J.E.Debreczeni,A.Bullock,A.Amos,P.Savitsky,A.Barr,N.Burgess, M.Sundstrom,J.Weigelt,C.Arrowsmith,A.Edwards,S.Knapp

Key ref:

A.N.Bullock et al. (2006). Crystal structure of the SOCS2-elongin C-elongin B complex defines a prototypical SOCS box ubiquitin ligase. Proc Natl Acad Sci U S A, 103, 7637-7642. PubMed id: 16675548 DOI: 10.1073/pnas.0601638103

Date:

14-Dec-05 Release date: 22-Feb-06

Protein chain

O14508  (SOCS2_HUMAN) -  Suppressor of cytokine signaling 2

Seq: 198 a.a.

Struc: 153 a.a.

Protein chain

Q15370  (ELOB_HUMAN) -  Transcription elongation factor B polypeptide 2

Seq: 118 a.a.

Struc: 103 a.a.

Protein chain

Q15369  (ELOC_HUMAN) -  Transcription elongation factor B polypeptide 1

Seq: 112 a.a.

Struc: 80 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: nucleus (3 terms)
• Biological process: intracellular signal transduction (10 terms)
• Biochemical function: protein binding (1 term)

DOI no: 10.1073/pnas.0601638103

Proc Natl Acad Sci U S A 103:7637-7642 (2006)

PubMed id: 16675548

Crystal structure of the SOCS2-elongin C-elongin B complex defines a prototypical SOCS box ubiquitin ligase.

A.N.Bullock, J.E.Debreczeni, A.M.Edwards, M.Sundström, S.Knapp.

ABSTRACT

Growth hormone (GH) signaling is tightly controlled by ubiquitination of GH receptors, phosphorylation levels, and accessibility of binding sites for downstream signaling partners. Members of the suppressors of cytokine signaling (SOCS) family function as key regulators at all levels of this pathway, and mouse knockout studies implicate SOCS2 as the primary suppressor. To elucidate the structural basis for SOCS2 function, we determined the 1.9-A crystal structure of the ternary complex of SOCS2 with elongin C and elongin B. The structure defines a prototypical SOCS box ubiquitin ligase with a Src homology 2 (SH2) domain as a substrate recognition motif. Overall, the SOCS box and SH2 domain show a conserved spatial domain arrangement with the BC box and substrate recognition domain of the von Hippel-Lindau (VHL) tumor suppressor protein, suggesting a common mechanism of ubiquitination in these cullin-dependent E3 ligases. The SOCS box binds elongin BC in a similar fashion to the VHL BC box and shows extended structural conservation with the F box of the Skp2 ubiquitin ligase. A previously unrecognized feature of the SOCS box is revealed with the burial of the C terminus, which packs together with the N-terminal extended SH2 subdomain to create a stable interface between the SOCS box and SH2 domain. This domain organization is conserved in SOCS1-3 and CIS1, which share a strictly conserved length of their C termini, but not in SOCS4, 5, and 7, which have extended C termini defining two distinct classes of inter- and intramolecular SOCS box interactions.

Selected figure(s)

Figure 2.
Comparative structural interactions and conservation of the SOCS box, BC box, and F box. (A) SOCS2 binds elongin C (electrostatic surface shown) in a hydrophobic interface of ≈2,200 Å^2 (for clarity, elongin B is not shown). Deep pockets accommodate residues from SOCS2 H1 (L163 and C167). (B) The three core helices of the SOCS box (red) show a remarkable structural conservation with the VHL BC box (yellow) and Skp2 F box (blue), forming a common structural motif to link E3 substrate recognition domains with the ubiquitin ligase complex. (C) The crystal structure of the Skp2-Skp1–Cul-1–Rbx1 ternary complex provides a template for the study of SOCS box–elongin C binding to Cul-5 (38). Because of different packing arrangements in their respective complexes, Skp1 shows structural and functional similarity to elongin C and SOCS2 H1, whereas H1 from Skp2 provides equivalence to SOCS2 H3 [consistent with previous Skp2-Skp1 comparison with VHL (39)]. SOCS2 P184 (shown in space-fill) occurs at the likely Cul-5 interface and terminates the “LPXP” cullin box. Mutation of this position in SOCS1 determines Cul-5 interaction (16).

Figure 4.
Unpredicted packing arrangements and burial of the SOCS2 N and C termini. (A) The side chain of V198 at the C terminus packs into a deep pocket in the back of the SH2 domain, and the terminal carboxyl forms hydrogen bond interactions with W48 (SH2) and Y194 (SOCS box). This conformation is stabilized by R168, which is strictly conserved within the SOCS family but not within the VHL BC box or Skp2 F box. (B) The ESS forms a single amphipathic helix (blue) that packs between the SH2 (orange) and SOCS box (red) domains with hydrophobic and electrostatic interactions, respectively, that bury a surface area of ≈1,200 Å^2.

Figures were selected by the author.