Structure Study of Small Heat Shock Protein 27
Abstract
Molecular chaperones are a class of oligomeric proteins that play a critical role in preventing the aggregation of non-native protein so that these proteins can later be refolded. Chaperones are ubiquitously expressed in all the kingdoms of life where their function is to counteract cellular stress and to maintain protein homeostasis. One subgroup of molecular chaperones is characterized by low molecular weight and are termed small heat shock proteins. The focus of the proposed research is the small heat shock protein 27 (Hsp27). Hsp27 is an ATP independent chaperone that is overexpressed in response to heat shock, radiation damage, oxidative damage, or other cellular stress in order to preserve protein homeostasis. Notably, there is an oligomeric reshuffling of Hsp27 from large oligomers to functional dimers under stressful conditions. Phosphorylation at three serine residues, 15, 78, 82 initiate the dynamic equilibrium change from large oligomeric complexes to much smaller dimeric subunits. Accumulation of misfolded protein causes numerous diseases that impacts the daily life of millions of individuals. For example, the misfolding or aggregation of microtubule associated protein Tau, and neuron associated alpha-synuclein are the pathological hallmarks for Alzheimer’s and Parkinson disease, respectively. Studies have suggested a significant role of Hsp27 in inhibiting the aggregation of both Tau and alpha-synuclein. The contact area between Hsp27 and its client proteins Tau and alpha-synuclein has been characterized by a variety of biophysical techniques that enhance our understanding neurotherapeutics. However, a high-resolution atomic structure of the monomeric full length Hsp27 still remains ambiguous because of the struggles in obtaining a homogeneous purified product for reconstruction and by the fact that the protein has intrinsic disorder. This intrinsic disorder is a functional attribute of a large portion of the N-terminal and C-terminal regions. This project aims to apply cryo-EM 3D reconstruction techniques to elucidate a high-resolution structure of human Hsp27 in complex with its substrates Tau and alpha-synuclein with the idea that the association with substrate will stabilize previously disordered regions in Hsp27.
Subject Area
Chemistry|Molecular chemistry|Biochemistry
Recommended Citation
Li, Zhaobo, "Structure Study of Small Heat Shock Protein 27" (2023). ETD Collection for University of Texas, El Paso. AAI30493172.
https://scholarworks.utep.edu/dissertations/AAI30493172