Protein folding, misfolding and

Protein Folding, Misfolding and Aggregation Classical Themes and Novel Approaches... 

C. M. Dobson (2004) Principles of protein folding, misfolding and aggrega-tion.5emm. Cell. Dev. Biol. 15, pp. 3-16... 

Squire,J. (1981). The Structural Basis of Muscle Contraction. Plenum Press, New York. Stefani, M., and Dobson, C. M. (2003). Protein aggregation and aggregate toxicity New insights into protein folding, misfolding diseases and biological evolution. J. Mol. Med. 81, 678-699. 

Abnormal accumulation of ubiquitinated intracellular proteinadous indusions is characteristic of the s-IBM phenotype, thus s-EBM, similarly to Alzheimer and Parkinson disease, is considered a "conformational disorder," caused by protein un-folding/misfolding and associated with formation of proteinadous indusion bodies (reviewed in [1-4]). Similarly to Alzheimer and Parkinson brains, the sequence of the detrimental pathologic events comprising cellular degeneration in s-IBM musde fibers is not yet weU delineated. However, several aspects of the s-EBM intra-muscle-fiber pathogenic cascade are being uncovered and their causative mechanisms elucidated. 

Jaenicke, R. (1995). Folding and association versus misfolding and aggregation of proteins. Philos. Trans. R. Soc. Lond. B Biol. Sci. 348, 97-105. 

Proteins translated on the RER generally fold and assemble into subimits in the ER before being transferred to the Golgi apparatus. Other proteins fold in the cytoplasm. Molecular chaperones (proteins such as calnexin and BiP) assist in this process of protein folding. Proteins that are misfolded are targeted for destruction by ubiquitin and digested in cytoplasmic protein-digesting complexes called proteasomes. 

King, J., Haase-Pettingell, C., and Gossard, D. (2002). Protein folding and misfolding. American Scientist, 90, 445—453. 

Protein folding is a complex, trial and error process that can sometimes result in improperly folded molecules. These misfolded proteins are usu ally tagged and degraded within the cell (see p. 441). However, this qual ity control system is not perfect, and intracellular or extracellular aggregates of misfolded proteins can accumulate, particularly as individ uals age. Deposits of these misfolded proteins are associated with a number of diseases including amyloidoses. 

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