Dynamics of the SPRY domain-containing SOCS box protein 2: Flexibility of key functional loops
- Author(s)
- Yao, SG; Liu, MS; Masters, SL; Zhang, JG; Babon, JJ; Nicola, NA; Nicholson, SE; Norton, RS;
- Details
- Publication Year 2006-12,Volume 15,Issue #12,Page 2761-2772
- Journal Title
- PROTEIN SCIENCE
- Publication Type
- Journal Article
- Abstract
- 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 b-sheets for the B30.2/SPRY domain but show differences located mainly at one end of the beta-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 (15)N 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.
- Publisher
- JOHN WILEY & SONS INC
- Keywords
- N-15 NMR RELAXATION; NORMAL-MODE ANALYSIS; BACKBONE DYNAMICS; ROTATIONAL DIFFUSION; CHEMICAL-EXCHANGE; MOLECULAR-DYNAMICS; TERMINAL DOMAIN; BINDING; SPECTROSCOPY; SSB-2
- Publisher's Version
- https://doi.org/10.1110/ps.062477806
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2006-12-01 12:00:00