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Proteine con folding errato sono coinvolte in malattie che evolvono molto lentamente Una placca amiloide in Alzheimer’s è composta da un ammasso di filamenti di proteine
Proteine con folding errato sono coinvolte in malattie che evolvono molto lentamente • Improper protein folding (misfolding) can lead to the formation of disordered (amorphous) or ordered (amyloid fibril) aggregates. • transmissible spongiform encephalopathies • prion diseases • Parkinson's disease • Lewy body variant of Alzheimer's disease • diffuse Lewy body disease • dementia with Lewy bodies • multiple system atrophy • neurodegeneration with brain iron accumulation type I. • familial amyloid polyneuropathy (FAP) • familial amyloid cardiomyopathy (FAC) • familial central nervous system amyloidosis • senile systemic amyloidosis (SSA) • Amyloidosis (Alzheimer disease) etc. Membrane proteins represent at least 30% of the all currently sequenced genomes and represent 60 percent of drug targets.
Lipid-Assisted Protein Folding Lipids act as molecular chaperones in folding of proteins Lipids act as molecular chaperones in folding of proteins LacY E. coli LacY assembled in a PE-lacking mutant ( pssA null mutant) only carried out facilitated but not active transport of substrate and misfolding of domain P7 (P7 is denatured) Monoclonal antibody Proper folding did NOT occur by addition of PE Changing the lipid composition of the membrane can reverse topology of a polytopic membrane protein, and lipids composition is a determinant of TM orientation