DEFECTIVE PROTEIN-FOLDING AS A BASIS OF HUMAN-DISEASE

The ability of a polypeptide to fold into a unique, functional, three- dimensional structure in vivo is dependent upon its amino acid sequenc e and the function of molecular chaperone proteins and enzymes that ca talyse folding. Intense study of the physical chemistry and cell biolo gy of folding have greatly aided our understanding of the mechanisms n ormally employed. Evidence is accumulating that many disease-causing m utations and modifications exert their effects by altering protein fol ding. Here we discuss the pathobiology of these processes.