This is a summary of our findings into the tau protein.

 

             Initially, the accession number P10636 resulted in 9 human tau isoforms in a Uniprot search.  These were found to be Tau-PNS, Tau-A , Tau-B , Tau-C, Tau-D, Tau-E, Tau-F and Tau-G. Despite Uniprot’s search identifying 9 isoforms , only 8 were identified in the BLAST search that was subsequently completed. A multiple sequence alignment was carried out to identify conserved regions between human tau isoforms and it’s respective homologues. All tau homologues display highly-conserved tubulin-binding repeats at the C-terminus, required for microtubule polymerization. In order to analyse the evolutionary relationship between tau homologues, we investigated a cladogram.

 

            Tau is one of the vertebrate microtubule-associated protein in the MAP2/Tau family, which additionally includes MAP2 and MAP4 and other homologues. The functions of Tau, MAP2 and MAP4 from human, mouse and monkey were compared and high similarity is idenfitied in the regulation of microtubule dynamics and promotion of microtubule assembly and stability.

 

          Multiple structure-prediction servers were then utilised, in an effort to uncover the hypothesized structure of Tau. Jpred, SWISS-MODEL and PSIPRED predicted tau as a protein with random beta-sheets throughout the molecule, and an alpha helix at C-terminus. Overall, the predicted models show a lot of secondary structure present, which is inconsistent with scientific literature surrounding tau. Therefore, this demonstrates an area in which further research could be undertaken into the tau protein.

 

            Throughout the molecular exploration it became apparnent that tau is heavily implicated in numerous neurodegenerative diseases, such as Alzheimer’s disease. This is another area , where more research could be undertaken especially due to the increasing prevalence of neurodegenerative diseases.

 

            Due to the disrepancies surrounding tau’s structure, advice was sought from Dr Rohan de Silva to aid our understanding, and for this we would like to acknowledge his guidance.