Protein Folding in Health & Disease Flashcards
(36 cards)
What factors restrict the number of conformations that an amino acid chain can fold in to?
- the rigidity of the peptide bond limits the flexibility of the chain
- the physical and chemical properties of the sidechains restricts the number of stable options
In protein folding, what structures will form first?
Secondary structures
Stabilising forces then retain these
What do the secondary structures form in protein folding?
They create a core structure from which the remaining process proceeds
How does the process of protein folding lead to a more stable conformation forming?
Less stable structures unravel and alternative structures form in quick succession
This occurs until a more stable conformation occurs
What conformation will the protein finally fold into?
The conformation that has the lowest energy level
In the unfolded form, the protein is in the highest energy level
What contains all the information needed to ensure correct protein folding?
What is the problem with this?
The amino acid sequence
However, within cells high protein concentrations and the presence of other biomolecules can interfere
What is the role of chaperone proteins?
What are the 2 types?
They are present in cells to facilitate protein folding
- molecular chaperones
- chaperonins
What is the role of molecular chaperones?
They bind to short segments of protein and help that particular area to fold correctly
What is the role of chaperonins?
They form folding chambers (protein barrels) which provide a stable environment to encourage correct folding
What happens if proteins are not folded correctly?
They will not function normally, if at all
What type of protein misfolding causes cystic fibrosis and phenylketonuria?
Mutations which cause proteins to be unable to fold into an active conformation
Lack of the proteins gives the symptoms of the disease
What happens if misfolded proteins accumulate?
They may hinder normal cellular processes and damage cells
How may a misfolded protein act as an infectious agent?
It causes conformational changes in other proteins
This damages previously normal cellular proteins
It may lead to a damaging accumulation of aggregated protein
What do protein misfolding diseases result in?
What causes this?
Aggregation of proteins and cell death
They are caused by formation of insoluble aggregates, rich in B-pleat sheet, of previously soluble proteins
What is an amyloid disease?
What happens?
Fragments of normal proteins produce amyloid fibres
The build up of abnormal protein amyloid makes it difficult for organs and tissues to function properly
What is a prion disease?
This occurs when an infectious protein agent causes a conformational change in a normal protein
What are examples of amyloid and prion diseases?
Amyloid: Alzheimer’s
Prion: Creutzfelt-Jacob, BSE and scrapie
What is a prion?
A type of protein that can trigger normal proteins in the brain to fold abnormally
What type of disease is Alzheimer’s disease?
How is it cured?
It is a progressive dementia
There is no cure and it eventually causes death
What are some of the symptoms of Alzheimer’s disease?
- memory loss
- loss of language ability
- loss of the ability to manipulate visual information
- poor judgement
- confusion
- mood swings and restlessness
When comparing the brain of an Alzheimer’s patient to a healthy patient, what is visible?
There is an obvious loss of neurones in the cerebral cortex
What causes Alzheimer’s disease?
A fragment from a normal membrane protein accumulates after it is cleaved by proteases
This is the amyloid precursor protein
It forms A-beta once cleaved
What is the structure of A-beta protein like?
It contains large amounts of B-pleated sheet structure
What happens once the amyloid precursor protein is cleaved to A-beta?
The protein aggregates and forms insoluble fibrils of amyloid B protein in the brain
