Structural and functional characterization of a conserved region in the disordered N-terminal domain of SOCS4 and SOCS5 — ASN Events
  1. Schedule
  2. Session Twelve - Poster Session D including Happy Hour & Trade Display
  3. Structural and functional characterization of a conserved region in the disordered N-terminal domain of SOCS4 and SOCS5

Structural and functional characterization of a conserved region in the disordered N-terminal domain of SOCS4 and SOCS5 (#428)

Indu R Chandrashekaran 1 , Biswaranjan Mohanty 1 , Charles A Galea 1 , Edmond Linossi 2 3 , Zhi-Ping Feng 2 3 , Jeffrey J Babon 2 3 , Sandra E Nicholson 2 3 , Raymond S Norton 1
  1. Monash Institute of Pharmaceutical Sciences, Parkville, VIC, Australia
  2. Walter and ELiza Hall Institute of Medical Research, Parkville, VIC, Australia
  3. Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia

Suppressors of cytokine signalling (SOCS) are involved in negative feedback inhibition of cytokine signaling cascade. The SOCS family, consisting of eight intracellular proteins, shares a common domain organization, with an N-terminal domain of variable length, a central SH2 domain and a conserved C-terminal SOCS box [1]. Recent studies have helped define the structure and role of the SH2 domain and SOCS box motif of the SOCS proteins, but the structure and function of the N-terminal domains of these proteins remain poorly characterized [2]. We have analysed the structural features of the N-terminal domains of the mammalian SOCS proteins and identified a very highly conserved segment within the N-terminal domain of SOCS4 and SOCS5; the high degree of sequence conservation of this region across different species implies an important functional role [3]. In order to understand the structural and functional roles of this region, regions of mouse SOCS4 (residues 86-155, mSOCS486-155) and SOCS5 (residues 175-244, mSOCS5175-244) were expressed in bacteria. The conformational preferences of mSOCS486-155 and mSOCS5175-244 in solution were characterized using multidimensional heteronuclear NMR spectroscopy. Sequence-specific assignments were made for mSOCS486-155. Interactions of this conserved region of SOCS4 and SOCS5 with its potential binding partners were also investigated using NMR spectroscopy and surface Plasmon resonance. The results from this study provide insights into the function of the N-terminal domain of SOCS4 and SOCS5 and their role in the regulation of cytokine signalling. 

  1. Hilton, D.J. et al. (1998) Proc. Natl. Acad. Sci. U S A. 95, 114-119.
  2. Babon, J.J. et al. (2006) Mol.Cell 22, 205-216.
  3. Feng, Z.P. et al (2012) Proteins 80,946-957.