Defective folding and rapid degradation of mutant proteins is a common disease mechanism in genetic disorders.

Abstract

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.

• Authors: N Gregersen, P Bross, M M Jørgensen, T J Corydon, B S Andresen
• Journal: Journal of inherited metabolic disease (J Inherit Metab Dis) Vol. 23 Issue 5 Pg. 441-7 (Jul 2000) ISSN: 0141-8955 [Print] United States
• PMID: 10947197 (Publication Type: Journal Article, Review)

Chemical References

• CFTR protein, human
• Proteins
• Cystic Fibrosis Transmembrane Conductance Regulator
• Acyl-CoA Dehydrogenases
• Acyl-CoA Dehydrogenase

Topics

• Acyl-CoA Dehydrogenase
• Acyl-CoA Dehydrogenases (deficiency)
• Cystic Fibrosis (genetics, metabolism)
• Cystic Fibrosis Transmembrane Conductance Regulator (chemistry, genetics, metabolism)
• Cytosol (metabolism)
• Endoplasmic Reticulum (metabolism)
• Genetic Diseases, Inborn (genetics, metabolism)
• Humans
• Mitochondria (metabolism)
• Mutation
• Phenylketonurias (genetics, metabolism)
• Protein Conformation
• Protein Folding
• Proteins (chemistry, genetics, metabolism)