BIOLOGY 2B03 Chapter Notes - Chapter 2: Endoplasmic Reticulum, Chaperonin, Protein Folding
17 Jun 2018
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BIOLOGY 2B03 - Module 2 Lecture I
Correcting Misfolding: Chaperones
Three Options when Protein Fail to Fold Correctly:
1) To assist protein folding using the machinery within the cell
- Mechanisms that assist protein folding employs the same principle: to
prevent inappropriate interactions
2) Molecular Chaperones and Chaperonin Complexes
3) If the protein ultimately cannot be folded, aggregates can form; Protein
Degradation
Two Types of Chaperones
General Principle: to prevent inappropriate interactions between amino acids to increase
the efficiency of protein folding
Two Classes:
1) Monomeric molecular chaperones
2) Multimeric chaperonin complex
● Both of these assist protein folding in essentially the same way
○ They help proteins to fold by preventing the formation for incorrect
folding within the molecules
○ Or, of inappropriate associations with other proteins
○ These mechanisms are ubiquitous
○ Not specific to to a subset of proteins, but can assist many different
proteins with distinct structures and functions
Molecular Chaperones
Molecular Chaperones: monomeric proteins; bind to hydrophobic amino acid residues on
a polypeptide and prevent the protein from forming incorrect folds caused by
hydrophobic interaction
Hsp70 (Heat Shocking Protein): first identified as proteins that are expressed at high
levels under conditions of stress (ex. High temperature)
● Protein’s denaturation at high temperature; cells respond by making more heat
shock proteins to refold various proteins in the cell.
● Ex) BiP in endoplasmic reticulum, DnaK in bacterial cells
Hsp70 Family of Heat Shock Proteins
Two Substrates
● The nucleotide-binding domain
● The substrate-binding domain
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Mechanism
1) The substrate will be an unfolded protein/nascent protein that is just leaving the
ribosome (unfolded)
2) Its hydrophobic residues are exposed to aqueous cytosol
3) The hydrophobic residues on Hsp70 bind to the protein’s hydrophobic residues
instantly
4) ATP hydrolysis to ADP; changing the conformation of the Hsp70 chaperone
● Concomitantly changes the relative shape of the target protein; allowing it
to fold properly
● Simulated by co-chaperones: DNAJ or Hsp40
● ATP hydrolysis assisted by exchange factor: GrpE or BAG1
5) A new ATP comes in to fill the nucleotide-binding domain
6) The folded protein is released and the Hsp70 is ready to bind to another
unfolded protein
Chaperonins
Is a large complexes, macromolecular complexes containing many different different
proteins.
● To form chamber or a barrel
○ Barrel: the region in which an unfolded protein fold in isolation
● Includes TCiP and GroEL
○ TCiP: proteins found in cytosol
○ GroEL: found in bacteria and chloroplast organelles
● Allows the newly synthesized polypeptides to fold without interference from
macromolecules
Folding Chambers of Chaperonins
The chaperonin complex consists of two large subunits:
● GroEL: large subunits that are attached to one
another at their bases
○ Hollow chamber that forms an isolation
chamber or folding chamber
● GroES: open or cap each of the tops of the
chambers; small subunit
Folding Occurs Within the Chaperonin
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find more resources at oneclass.com
Document Summary
Three options when protein fail to fold correctly: to assist protein folding using the machinery within the cell. Mechanisms that assist protein folding employs the same principle: to prevent inappropriate interactions. 3) if the protein ultimately cannot be folded, aggregates can form; protein. General principle: to prevent inappropriate interactions between amino acids to increase the efficiency of protein folding. Two classes: monomeric molecular chaperones, multimeric chaperonin complex. Both of these assist protein folding in essentially the same way. They help proteins to fold by preventing the formation for incorrect folding within the molecules. Or, of inappropriate associations with other proteins. Not specific to to a subset of proteins, but can assist many different proteins with distinct structures and functions. Molecular chaperones: monomeric proteins; bind to hydrophobic amino acid residues on a polypeptide and prevent the protein from forming incorrect folds caused by hydrophobic interaction.
