protein folding
Terms
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- diseases that resulted from protein folding gone wrong
- mad cow, alzheimers, cystic fibrosis, emphysema, cancer
- proteins
- fundamental components of all living cells
- misfolded proteins
- poison the cells around it
- christian anfinsen
- if proteins become unfolded then they fold back into the propper shape, no shaper/folder needed
- chaperones
- keep proteins from getting off the right folding path
- anfinsens theory to protein folding diseases
-
protiens will fold into a wrong shape
chaperones help fold - certain diseases are characterized by...
- extensive protein deposits in certain tissues
- alzheimer noted that...
- neurofibrilary tangles and neuritic plaaque (dieseases that have extensive nerve cell death) are specific to alzheimers
- key to a-helix and b-sheet
- hydrogen bond
- number of amino acids for each turn of the a-helix
- 3.6 amino acids
- a-helix
- right hand spiral stabilized by hydrogen bonds btwn each amino acid (nitrogen atom and the oxygen atom) of the fourth one up the chain
-
b-sheet
parallel
antiparallel -
flat with sides of the chain sticking out on alteranate sides, stabilized by hydrogen bonds btwn nitrogen and oxygen atoms, amino acid chains run alongside each other
parallel- run in same direction
antiparallel- alternate chains run in opposite directions -
antiparallel sheets
b-turn -
often formed by one chain looping back on itself
b-turn- the 1 to 3 amino acids linking 2 strands - partially folded chains
- fold in a fraction of a second
- P22
- virus that infects bacteria
- high temp. sensitive mutations
- one amino acid altered and turns into insoluble gunk, able to analyze bacterial cells to see what went wrong with the folding
- FAP
- peripheral nerves and other organs are damaged by deposists of amyloid-type protein, rare disease, transthyretin mutations (b-sheets, identical amino acid chains) 50 different mutations
- transthyretin aggregation
- monomeric unfolding intermediate
- transthyretin
- normal transthyretin, when protein is broken down it turns to insoluble gunk that poisons the tissues where it is deposited
- alzheimers afflicts...
-
10% of those over 65
50% of those over 85
kills 10,000 each year
costs $82.7 billion
amyloid precursor protein mutations develop alzheimers as early as 40 - neuritic plaque
- pathway leading to alzheimers
- alzheimers disease is limited...
- to old people b/c the process takes a long time, have the normal amyloid precursor protein
- apoE
- trasports cholesterol and other fatty materials in the blood stream, rapid formation of plaque
- AB plays a major roll in __ disease
- alzheimers
- prions
- protein particles, pure protien that contain neither DNA or RNA, self replicating (own chaperone)
- mad cow (scrapie, creutzfeldt-jacob)
- diseases transmitted by prions
- cystic fibrosis
- lack of protein that regulates the transport of the chloride ion across the cell membrane
- cystic fibrosis hinders...
- seperation of the transport regulator protein from one of its chaperones, final steps in folding cant occur, normal amounts of active protein arent produced
- emphysema
- buildup of a crucial folding intermediate leads to aggregation which deprives some of enough circulating a1 antitrypsin to protect lungs
- purpose of studying diseases
- find ways to treat it
- p53
- involved in 40% of all human cancers, prevents cells from becoming cancerous
- p53 (2 clases)
-
1.keeps protein from binding to DNA
2.makes folded form of protein less stable - TIP and the thyroid hormone
- can stabilize transthyretin and is a treatment for FAP
- once folding is complete...
- chaperone will leave its protein to help another
- how many chaperones can there be
- several
- chaperones primary function
- prevent aggregation