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Defective folding and rapid degradation of mutant proteins is a common disease mechanism in genetic disorders
Author(s) -
Gregersen N.,
Bross P.,
Jørgensen M. M.,
Corydon T. J.,
Andresen B. S.
Publication year - 2000
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1023/a:1005663728291
Subject(s) - proteases , protein folding , biology , phenotype , point mutation , mutation , mutant protein , disease , clinical phenotype , mechanism (biology) , protein degradation , genetics , microbiology and biotechnology , biochemistry , medicine , enzyme , gene , philosophy , epistemology
Many disease‐causing point mutations do not seriously compromise synthesis of the affected polypeptide but rather exert their effects by impairing subsequent protein folding or stability of the folded protein. This often results in rapid degradation of the affected protein. The concepts of such ‘conformational disease’ are illustrated by reference to cystic fibrosis, phenylketonuria and short‐chain acyl‐CoA dehydrogenase deficiency. Other cellular components such as chaperones and proteases, as well as environmental factors, may combine to modulate the phenotype of such disorders and this may open up new therapeutic approaches.