2020 Virtual undergraduate Research symposium

Structural Studies of Amyloid Proteins


PROJECT NUMBER: 31

AUTHOR: Colista West, Chemistry | MENTOR: Judith Klein-Seetharaman, Chemistry

 

ABSTRACT

The protein α-synuclein (aS), implicated in Parkinson’s disease and other neurodegenerative disorders, has suspected structural and functional homology with the 14-3-3 family of chaperones. To find evidence for structural homology, we predicted amyloidogenic propensity and intrinsic structural disorder, relative to regions of homology, between aS and 14-3-3 zeta (Z) isoform. We submitted available aS and Z sequences to AmylPred2, PASTA 2.0, and PONDR. Previous alignments suggested homology between residues 1-61 in aS and 105-166 in Z. PONDR predicts residues 1-10 in aS and 1-93 in Z as disordered— the crystal structure of Z indicates this region is structured, namely helical. Amyloid predictors suggest residues 62-80 in aS, and 171-180 in Z, have high amyloidogenic propensity, which may functionally extend the similarity between the proteins. Using BLAST, we identified another region of homology between residues 129-135 in aS and 207-213 in Z, which are predicted by PONDR to be unstructured in both proteins. The crystal structure of Z also shows no density for this region. Based on this computational analysis, we hypothesize that the helical N-terminal region in Z protects it from being as aggregation prone as aS despite the presence of the highly amyloidogenic peptide between the N and C-terminus.

 

VISUAL PRESENTATION

 

AUTHOR BIOGRAPHY

Colista is currently a senior in Chemistry at Colorado School of Mines. Her multidisciplinary research is focused on understanding the role that protein structure plays in Parkinson’s disease pathology. She is primarily interested in the chaperone activity of alpha-synuclein and its relationship and interactions with other, non-disease related chaperone proteins expressed in the brain. Colista hopes to continue neuroscience related research in grad school and future pursuits.

 


5 Comments

  1. It looks great!!

    • Thank you!

  2. Research into Parkinson’s disease is immensely important. Your maternal grandfather and his son, your uncle, both had/have this disease. Thank you for your contribution to the reasearch base.

  3. Colista – Well done! You did a nice job presenting information in a way that was easy to follow and understand without being overwhelming. Keep after it!

    • Thank you for taking the time to read through my project!

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