Molecular modeling and molecular dynamics simulations based structural analysis of the SG2NA protein variants

BMC Research Notes

Shyamal K Goswami¹  Abhinav Grover²  Chetna Tyagi²  Sangeeta Soni¹ 

[1] School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India;School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India

关键词: Striatin;    Disorder prediction;    Molecular dynamics simulations;    Molecular modeling;    SG2NA;   

Others  :  1131927
DOI  :  10.1186/1756-0500-7-446

 received in 2014-03-11, accepted in 2014-07-01,  发布年份 2014

【 摘 要 】

Background

SG2NA is a member of the striatin sub-family of WD-40 repeat proteins. Striatin family members have been associated with diverse physiological functions. SG2NA has also been shown to have roles in cell cycle progression, signal transduction etc. They have been known to interact with a number of proteins including Caveolin and Calmodulin and also propagate the formation of a multimeric protein unit called striatin-interacting phosphatase and kinase. As a pre-requisite for such interaction ability, these proteins are known to be unstable and primarily disordered in their arrangement. Earlier we had identified that it has multiple isoforms (namely 35, 78, 87 kDa based on its molecular weight) which are generated by alternative splicing. However, detailed structural information of SG2NA is still eluding the researchers.

Results

This study was aimed towards three-dimensional molecular modeling and characterization of SG2NA protein and its isoforms. One structure out of five was selected for each variant having the least value for C score. Out of these, m35 kDa with a C score value of −3.21was the most poorly determined structure in comparison to m78 kDa and m87 kDa variants with C scores of −1.16 and −1.97 respectively. Further evaluation resulted in about 61.6% residues of m35 kDa, 76.6% residues of m78 kDa and 72.1% residues of m87 kDa falling in the favorable regions of Ramchandran Plot. Molecular dynamics simulations were also carried out to obtain biologically relevant structural models and compared with previous atomic coordinates. N-terminal region of all variants was found to be highly disordered.

Conclusion

This study provides first-hand detailed information to understand the structural conformation of SG2NA protein variants (m35 kDa, m78 kDa and m87 kDa). The WD-40 repeat domain was found to constitute antiparallel strands of β-sheets arranged circularly. This study elucidates the crucial structural features of SG2NA proteins which are involved in various protein-protein interactions and also reveals the extent of disorder present in the SG2NA structure crucial for excessive interaction and multimeric protein complexes. The study also potentiates the role of computational approaches for preliminary examination of unknown proteins in the absence of experimental information.

【 授权许可】

   
2014 Soni et al.; licensee BioMed Central Ltd.

【 图 表 】

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