Dynamics of the SPRY domain-containing SOCS box protein 2: Flexibility of key functional loops

Shenggen Yao, Ming S. Liu, Seth L. Masters, Jian Guo Zhang, Jeffrey J. Babon, Nicos A. Nicola, Sandra E. Nicholson, Raymond S. Norton

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13 Citations (Scopus)


The SPRY domain was identified originally as a sequence repeat in the dual-specificity kinase splA and ryanodine receptors and subsequently found in many other distinct proteins, including more than 70 encoded in the human genome. It is a subdomain of the B30.2/SPRY domain and is believed to function as a protein-protein interaction module. Three-dimensional structures of several B30.2/SPRY domain-containing proteins have been reported recently: murine SSB-2 in solution by NMR spectroscopy, a Drosophila SSB (GUSTAVUS), and human PRYSPRY protein by X-ray crystallography. The three structures share a core of two antiparallel β-sheets for the B30.2/SPRY domain but show differences located mainly at one end of the β-sandwich. Analysis of SSB-2 residues required for interactions with its intracellular ligands has provided insights into B30.2/SPRY binding specificity and identified loop residues critical for the function of this domain. We have investigated the backbone dynamics of SSB-2 by means of Modelfree analysis of its backbone 15N relaxation parameters and carried out coarse-grained dynamics simulation of B30.2/SPRY domain-containing proteins using normal mode analysis. Translational self-diffusion coefficients of SSB-2 measured using pulsed field gradient NMR were used to confirm the monomeric state of SSB-2 in solution. These results, together with previously reported amide exchange data, highlight the underlying flexibility of the loop regions of B30.2/SPRY domain-containing proteins that have been shown to be important for protein-protein interactions. The underlying flexibility of certain regions of the B30.2/SPRY domain-containing proteins may also contribute to some apparent structural differences observed between GUSTAVUS or PRYSPRY and SSB-2. Published by Cold Spring Harbor Laboratory Press.

Original languageEnglish
Pages (from-to)2761-2772
Number of pages12
JournalProtein Science
Issue number12
Publication statusPublished - Dec 2006
Externally publishedYes


  • N relaxation
  • B30.2/SPRY domain
  • Backbone dynamics
  • Conformational exchange
  • NMR
  • Normal mode analysis
  • SOCS protein
  • Translational diffusion

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