BIOL 4050U Study Guide - Midterm Guide: Dystroglycan, Alpha Helix, Frequent Urination
BIOL 4050-MIDTERM 2 NOTES
Lecture 4: Heat Shock Protein BGP-15 & Muscular Dystrophy
Protein folding can be dictated by primary amino acid sequence
Molecular chaperones: are proteins involved in proper folding of other proteins
Constantly active or stress induced
Misfolded protein can cause toxic affect
Aggregation with other proteins, reducing function
Neurodegenerative disease e.g. Alzheimer’s
Heat shock Protein (HSP): family of proteins that are chaperones induced by stimulus such as
heat, stress, toxin. HSP 72 inducible form
Heat shock cognate (HSC): facilitate proper folding of proteins emerging from ribosome, non-
stress
Facilitating in proper folding of new polypeptides emerging from a ribosome (HSC73)
HSP70/HSC73 is located in the cytoplasm and its function is to prevent protein aggregation, aids
in protein folding
72 is the inducible form
The number is the weight in kiladaltons
Heat shock protein can be induced to protect cells
HSF1, without this heat shot transcription won’t do anything
Transcription factors: assist in the process of transcription (expression of a gene)
With onset of stress, you get accumulation of unfolded protein
The whole complex dissociates
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HSF1 is liberated and free to move its way into the nucleus of the cell
In the nucleus it makes trimers and initiates transcription of the HSP
The rest of heat shock protein help to fold this Leads to expression of mRNA
One abundance of heat shock protein are made and aid in folding, and then they can reform
complex (negative feedback loop) shut down this process
Heat shock protein cellular stress response
1. During non-stress, HSP’s and heat shock factor 1 (HSF-1) are in complex
2. Stress causes disassociation of complex HSP’s bind to unfolded proteins
3. HSF-1 now free to move to nucleus
4. HSF-1 trimerizes and binds to heat shock element (HSE) of DNA
5. More HSP70 proteins are made to assist with stress eg. HSP70
6. Presence of new HSP’s bind HSF-1 and inhibit the response
HSP 70 members:
HSC 73 constantly active, fold native proteins
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HSP 72 stress induced, protects from protein miss folding
GRP 78
GRP 75
HSP72 structure
N-terminal ATPase domain: binds to ATP and hydrolyzes to ADP, change protein shape
Peptide (or Substrate) binding domain: affinity for neutral. Hydrophobic amino acid
residues. Binds multiple residues of many proteins
C-terminal domain: has alpha helix structure “lid”, tightens binding in presence of ADP
Muscular Dystrophy: disease characterized by progressive weakening/wasting of muscle tissue
9 different forms, Duchenne’s (DMD) is one of the most severe
DMD is X-linked (chromosome) mutation of dystrophin gene
Dystrophin is a cytoplasmic protein, anchors cytoskeleton filaments of muscle fibers to cell
membrane (sarcolemma and extracellular matrix
Muscle cytoskeleton: Microfilaments
Polymers composed of the protein actin
-3 vertebrate isoforms:
- Stretches out the length of fibrous muscles, provide means so muscles can short
- In more complex animals, It is used to contract skeletal muscles
Found in all eukaryotic cells
Often use the motor protein myosin
Movement arises from:
Actin polymerization (-actin-microfilaments)
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Document Summary
Lecture 4: heat shock protein bgp-15 & muscular dystrophy. Protein folding can be dictated by primary amino acid sequence. Molecular chaperones: are proteins involved in proper folding of other proteins. Heat shock protein (hsp): family of proteins that are chaperones induced by stimulus such as heat, stress, toxin. Heat shock cognate (hsc): facilitate proper folding of proteins emerging from ribosome, non- stress. Facilitating in proper folding of new polypeptides emerging from a ribosome (hsc73) Hsp70/hsc73 is located in the cytoplasm and its function is to prevent protein aggregation, aids in protein folding. Heat shock protein can be induced to protect cells. Hsf1, without this heat shot transcription won"t do anything. Transcription factors: assist in the process of transcription (expression of a gene) With onset of stress, you get accumulation of unfolded protein. Hsf1 is liberated and free to move its way into the nucleus of the cell. In the nucleus it makes trimers and initiates transcription of the hsp.
