Access Type

Open Access Dissertation

Date of Award

January 2019

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Chemical Engineering and Materials Science

First Advisor

Korosh Torabi

Abstract

A coiled-coil protein structure consists of two (in coiled-coil dimers) or more interacting α-helical strands that together form a left-handed supercoil structure. Many coiled-coil proteins are involved in significant biological functions such as the regulation of gene expression, known as transcription factors. Also coiled-coil structures entail unique mechanical properties critical to the function and integrity of various motor proteins, cytoskeletal filaments and extra-cellular matrix proteins. Engineering these transcription factors is also expected to create more efficient and practical solutions to treat neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and prion diseases, which are increasingly being realized to have common cellular and molecular mechanisms including protein aggregation.

The main objectives of our work are: a) to develop a model to predict the propensity of a protein sequence to form an isolated coiled-coil structure, and b) to investigate the selectivity of coiled-coils by studying protein-protein interactions. Control over protein-protein interaction specificity has a wide range of applications in synthetic biology such as protein labeling and purification (as high-specificity affinity tags or cognate pairs), drugs and toxin delivery and disease modulation. In naturally occurring proteins, specificity is achieved via a complex balance of various molecular-level energetic and entropic interactions. Such complexity makes any specificity prediction from the primary sequence data an extremely complicated task. Possibly, one of the simplest and most studied protein-protein interactions exists in coiled-coil structures.

Download

Share

COinS