skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Structural Basis for Phosphotyrosine Recognition by Suppressor of Cytokine Signaling-3

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 Angstroms 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.

Authors:
; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
914010
Report Number(s):
BNL-78578-2007-JA
TRN: US0801471
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Structure; Journal Volume: 14
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; 43 PARTICLE ACCELERATORS; AFFINITY; CRYSTAL STRUCTURE; PHOSPHOTRANSFERASES; PROTEINS; RESOLUTION; SPECIFICITY; TARGETS; TRANSCRIPTION; TRANSDUCERS; NSLS; national synchrotron light source

Citation Formats

Bergamin,E., Wu, J., and Hubbard, S.. Structural Basis for Phosphotyrosine Recognition by Suppressor of Cytokine Signaling-3. United States: N. p., 2006. Web. doi:10.1016/j.str.2006.06.011.
Bergamin,E., Wu, J., & Hubbard, S.. Structural Basis for Phosphotyrosine Recognition by Suppressor of Cytokine Signaling-3. United States. doi:10.1016/j.str.2006.06.011.
Bergamin,E., Wu, J., and Hubbard, S.. Sun . "Structural Basis for Phosphotyrosine Recognition by Suppressor of Cytokine Signaling-3". United States. doi:10.1016/j.str.2006.06.011.
@article{osti_914010,
title = {Structural Basis for Phosphotyrosine Recognition by Suppressor of Cytokine Signaling-3},
author = {Bergamin,E. and Wu, J. and Hubbard, S.},
abstractNote = {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 Angstroms 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.},
doi = {10.1016/j.str.2006.06.011},
journal = {Structure},
number = ,
volume = 14,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}