2HMH

Crystal structure of SOCS3 in complex with gp130(pTyr757) phosphopeptide.

Summary for 2HMH

• Entry DOI: 10.2210/pdb2hmh/pdb
• Descriptor: Suppressor of cytokine signaling 3, Interleukin-6 receptor beta chain (3 entities in total)
• Functional Keywords: socs3, gp130, ptyr, peptide complex, cytokine regulator
• Biological source: Mus musculus (house mouse); More
• Cellular location: Cell membrane ; Single-pass type I membrane protein : Q00560
• Total number of polymer chains: 2
• Total formula weight: 18332.27

Authors

Bergamin, E.,Wu, J.,Hubbard, S.R. (deposition date: 2006-07-11, release date: 2006-08-15, Last modification date: 2024-11-20)

Primary citation

Bergamin, E.,Wu, J.,Hubbard, S.R.
Structural basis for phosphotyrosine recognition by suppressor of cytokine signaling-3.
Structure, 14:1285-1292, 2006

PubMed Abstract: Suppressor of cytokine signaling (SOCS) proteins are indispensable negative regulators of cytokine-stimulated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathways. SOCS proteins (SOCS1-7 and CIS) consist of a variable N-terminal region, a central Src homology-2 (SH2) domain, and a C-terminal SOCS box. The N-terminal region in SOCS1 and SOCS3 includes the so-called kinase inhibitory region that has been shown to inhibit the catalytic activity of JAK2. Here, we present a crystal structure at 2.0 A resolution of the N-terminally extended SH2 domain of SOCS3 in complex with its phosphopeptide target on the cytokine receptor gp130. The structure reveals that major insertions in the EF and BG loops of the SOCS3 SH2 domain are responsible for binding to gp130 with high affinity and specificity. In addition, the structure provides insights into the possible mechanisms by which SOCS3 and SOCS1 inhibit JAK2 kinase activity.

PubMed: 16905102
DOI: 10.1016/j.str.2006.06.011

Experimental method

X-RAY DIFFRACTION (2 Å)