Role of Intermediate States in Protein Folding and Misfolding
Pp. 433-455 (23)
Roberto Santucci, Fabio Polticelli, Federica Sinibaldi and Laura Fiorucci
Most proteins fold into their native structure through defined pathways which
involve a limited number of transient intermediates. Intermediates play a relevant role in
the folding process; many diseases of genetic nature are in fact coupled with protein
misfolding, which favours formation of stable inactive intermediate species of a protein.
This review describes a number of diseases originated from protein misfolding and
briefly discusses the mechanism(s) responsible, at molecular level, for these
pathologies. It is also envisaged the native ⇄ molten globule transition since sometimes
the conversion of the native form into a compact intermediate state permits a protein to
carry out distinct physiological functions inside the cell. A non-native compact form of
cyt c, for example, is involved in the programmed cell death (apoptosis) after that the
protein is released from the mitochondrion; in addition, non-native forms of the protein
are involved in some of the disorders attributed to amyloid formation.
Alzheimer’s disease, amyloid fibrils, apoptosis, conformational
diseases, cystic fibrosis, cytochrome c, energy landscapes, folding pathways,
intermediate states, Levinthal paradox, misfolding, molten globule,
neurodegenerative diseases, phospholipids, protein folding.
Department of Clinical Sciences and Translational Medicine, University of Rome ‘Tor Vergata’, Via Montpellier 1, 00133 Rome, Italy.