Proteinopathies Flashcards
Loss of proteostasis contributes to the pathogenesis of many human pathologies, including
Alzheimer’s disease
how many stages of protein structure
3
protein X determines its function
shape
Proteinopathies:
accumulation of misfolded proteins resulting in aggregates, thereby gaining toxic activity or losing the normal function
why do proteins aggregate
cellular environment is highly crowded
6 features of Ubiquitin-proteasome system
- polyubiquitination
- polyUb-protein recognised by CAP
- polyUb removed
- protein unfolded
- protein threaded through proteasome
- proteolysis
2 features in a second structure protein
alpha helix
beta sheet
what is a 3rd structure protein
Stabilised by interactions between R groups
3 features in a 3rd structure protein
hydrophobic interactions between non-polar R groups
hydrogen bonds between polar R groups
disulfide bonds
what is an alpha helix
Results from H bonds forming between carbonyl oxygen atom of each peptide bond with the amide H atom from an amino acid 4 positions towards the C-terminus R groups face outwards, covering the helix
what is a beta sheet
Each strand is 5-8 amino acid residues
Hydrogen bonding between strands of polypeptide forms the planar sheet
The brains of people with AD have an abundance of two abnormal structures
- amyloid plaques in extracellular space
- neurofibrillary tangles in cytoplasm both are composed of misfolded proteins
what is Alzheimers disease
- common form of dementia
- Progressive and fatal
- affecting language, memory, and vision, as well as emotion and personality
what allele is involved in sporadic Alzheimers
ApolipoproteinE e4 allele
proteins present in early onset familial Alzheimers
Amyloid Precursor Protein (APP)
Presenilin -1, -2
Primary protein structure
