Protein folding, unfolding and misfolding: role played by intermediate States.
Most proteins fold into their native structure through well 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 due to formation of stable, inactive intermediate species of the protein. This review deals with a number of diseases associated with protein misfolding and briefly describes the mechanism(s) responsible, at molecular level, for such pathologies. It is also considered the (native <--> molten globule) transition, recently observed for some proteins, in which a native protein converts into a stable compact intermediate state able to carry out distinct physiological functions inside the cell. A non-native compact form of cyt c, for example, appears to have a role in the programmed cell death (apoptosis) after that the protein is released from the mitochondrion, and non-native forms of the same protein appear involved in some of the disorders attributed to amyloid formation.
Santucci
R
R
Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università di Roma Tor Vergata, Via Montpellier 1, 00133 Roma, Italy. santucci@med.uniroma2.it
Sinibaldi
F
F
Fiorucci
L
L
D000544:Alzheimer Disease / Q000209:etiology*; D006801:Humans; D007700:Kinetics; D009369:Neoplasms / Q000209:etiology*; D010300:Parkinson Disease / Q000209:etiology*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
D011506:Proteins