Dynamics of the SPRY domain-containing SOCS box protein 2: flexibility of key functional loops.
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 beta-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.
Yao
Shenggen
S
The Walter and Eliza Hall Institute of Medical Research, Parkville 3050, Victoria, Australia. syao@wehi.edu.au
Liu
Ming S
MS
Masters
Seth L
SL
Zhang
Jian-Guo
JG
Babon
Jeffrey J
JJ
Nicola
Nicos A
NA
Nicholson
Sandra E
SE
Norton
Raymond S
RS
D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000737:chemistry*; D004058:Diffusion; D004330:Drosophila; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D004268:DNA-Binding Proteins; C508499:SSB-2 protein, mouse