Mutation Hotspot Prediction, Structural Analysis & Stability Changes of Prion Protein Involved in Causing CJD

Author Name(s): Ankita Barik
Author Email: ankitasuchi258@gmail.com

Abstract

Creutzfeldt-Jakob disease (CJD) is a rare, degenerative, invariably fatal brain disorder. It affects about one person in every one million people per year worldwide. Creutfeldt-jakob disease is the most frequently seen type of prion diseases. The study on the role of prion protein and its involvement in the occurrence of prion protein is the point to be considered. In the current work the protein structural analysis and mutation prediction has been undertaken for prion protein. Focus was to identify the disorder regions which have maximum probability of mutation which was followed by the effect of mutation on these sites. The work included a series of steps, collection of the protein sequence from NCBI followed by domain analysis using SMART & GLOB-PLOT. STRING is a database of known and predicted protein-protein interaction which is used to identify the networking proteins for prion protein. The disordered /unstructured regions within a protein sequence were identified by DisEMBL. RONN is used for the prediction of protein disorder with the disorder probability predicted for each amino acid. I Mutant and Polyphen were the two major tools used for the study of effect of mutations on the stability and functions of the protein. For primary structure and secondary structure prediction PROTPARAM and SOPMA were applied. The three-dimensional structure of protein sequence was analysed using Phyre 2.

Keywords

CJD, Prion, SMART, GLOBPLOT, RONN, STRING, PROTPARAM, SOPMA

Introduction

The term “prion”is derived from proteinacious particle and refers to the pathogen that causes transmissible spongiform encephalopathy (TSEs).This small infectious particle is a disease-causing form a protein called cellular prion protein (Prpc) PRNP(PRION PROTEIN) is the human gene encoding for the major prion protein prp (for prion protein or protease-resistance protein).It is also known as CD230(cluster of differentiation 230). Prions are also unique and they don’t contain nucleic acid, unlike bacteria, fungi, viruses and pathogens. The normal prion protein is thought to be made up of flexible coils referred to as alpha helices, but in the abnormally folded form, these helix are stretched out into densely packed structures called beta sheets.

Conclusion

The above work was aimed to study in detail the sequence properties and the mutational possibility of the prion protein which is a cause of several diseases. The study included the identification of the most Mutable site on the protein i.e. the position 53 in the sequence. The effect of mutations to these site were also studied functionally and stability based. Functionally polyphen proved that any mutation to this site causes a probably damaging effect.

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