ABSTRACT
The functional behavior of a protein molecule is intimately and specically related to its spatial structure, its conformation. Enzymes, transport proteins and immunoproteins, become inactive when the conformation is perturbed. The structure-function relationship may be most dramatically demonstrated for proteins that are held responsible for so-called conformational diseases. The classical example is sickle cell anemia. Due to a slight, genetically determined, modication of its composition, the oxygen-transporting protein hemoglobin forms oblong aggregates causing morphological and physiological disruption of the erythrocytes. Patients suffer from severe anemia. Another class of conformational diseases shares the feature that the protein involved undergoes a misfolding leading to brillar structures that deposit in the tissue. Neurodegenerative diseases such as Parkinson’s, Alzheimer’s, and Creutzfeldt-Jakob’s disease are thus explained. The pathological conformation could follow from a genetic mutation. However, the conformation transition may as well occur in normal protein molecules, where it is triggered by exposure to the abnormal form. The pathological conformation then acts as a template for the conversion. The picture shows the prion protein in its normal conformation (left) and its misfolded conformation (right). Transformation of the normal into the misfolded form involves transition of α-helical structural elements (indicated by the spirals) into β-sheets (indicated by the arrows). The misfolded conformers associate to form aggregates that are held responsible for brain damage leading to symptoms of bovine spongiform encephalopathy (BSE, mad cow’s disease) and Creutzfeldt-Jakob’s disease in humans.
