NTU Undergraduates' research April 2014 - Biosciences | Page 132

CHAPERONES: IN-VIVO PROTEIN
FOLDING
Temidayo Sonukan
School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom

ABSTRACT
Molecular chaperones are proteins, expressed ubiquitously, which aid correct folding of a
polypeptide chain and prevent unwanted reactions such as aggregation. This thesis focuses on how
molecular chaperones promote the correct folding of proteins in vivo and how in correct folding of
proteins may affect the cell. Non-native proteins (U) are required achieve their native state (N), by
passing through conformational intermediates (I), in order them to perform their physiological
function. Stressors such as chemicals or heat may induce the proteins to misfold and/or aggregate.
Molecular chaperones minimize any unwanted reactions, arising from overcrowding or stress, which
may occur whilst the native state is being achieved. The two main type of chaperone families are the
heat shock proteins (HSPS) (e.g. sHSPs, HSP40s, HSP70s and HSP90s) and the chaperonins
(e.g. HSP60). The two types differ in their mechanism of action. HSPs bind to unfolded proteins via
binding to the protein’s exposed hydrophobic core, refolding the protein and then releasing the
appropriate conformation of substrate peptide. This process is ATP-dependent and goes through a
cycle of ATP hydrolysis for energy. Chaperonins, mostly, have the same ATP-dependent but the differ
in that they enclose the unfolded protein in their cavity and use cofactors as a “lid” to trap the
protein. Strong evidence suggests that chaperones are neuroprotective against neurodegenerative
diseases such as Parkinson’s (PD), Alzheimer’s (AD), Huntington’s (HD) and Creutzfeld-Jacob’s (CJD)
diseases.
Keywords: Molecular chaperones; Aggregation; Protein folding; Misfolding; Neurodegenerative disease