In silico analysis of detrimental mutation in EPHB2 gene causing Alzheimer’s disease
© Tayubi et al; licensee BioMed Central Ltd. 2014
Published: 2 April 2014
EPHB2 (Ephrin Receptor B2) are instrumental in signaling pathways like MAPK mediating tumour suppression, progenitor cell proliferation etc. [1, 2]. Previous research has investigated the possibility that disrupted EphB2- NMDA R binding is relevant to the development of Alzheimer’s disease (AD), a condition that is characterized by severe synaptic impairment. Hence it can be inferred the role of EPHB2 and associated single nucleotide polymorphism is essential in studying the signaling pathways as well as neurodevelopmental processes associated with it. Studying the impact of the protein and the associated non-synonymous SNPS can also decode the role of genetic variations with respect to the role of the protein in the signaling pathway as well as susceptibility towards the disease.
Materials and methods
The mutation results in a ddG of 2.86 kcal/mol, accessible cavity reduced in mutant protein. Residues Ile196 and Tyr122 are no longer contributing to the stability of the protein. The mutant protein is unstable compared to the native protein (Figure 1):
The mutation R80H is having adverse effects on the stability of the protein. It can be inferred from the results, the mutation affects the role of EPHB2. Further studies on its impact with its reactivity with NMDA receptor and role in the AD can be carried out.
- Cisse , et al: Reversing EphB2 depletion rescues cognitive functions in Alzheimer model. Nature. 2011, 469 (3): 47-52.PubMed CentralView ArticlePubMedGoogle Scholar
- Takasu , et al: Modulation of NMDA receptor-dependent Calcium influx and gene expression through EphB receptors. Science. 2002, 295 (5554): 491-495.View ArticlePubMedGoogle Scholar
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