Chaperones: Helping Protein Reach Their Proper Folded State Qi Bin P79

Curious finding In fruit fly larval When the temperature goes up from normal 25ºC to 32ºC activate A number of new sites on the giant chromosome

conclusion In every type of organism, from bacteria to plants and mammals Temperature goes up induce The expression of new genes This response is called the heat shock response and the protein which was produced during heat shock is called Heat Shock Protein(Hsp). PS: Hsps were found not only in heat shocked cells, but also at lower concentration in cells under normal condition

What is the function of these so-called Hsps? binding protein (Bip) promote protein assemblebinding protein (Bip) promote protein assemble Molecular chaperones Hsp60

Binding protein (Bip) promote protein assemble The discovery of Bip: A.In bacteriophage, a protein encoded by the bacterial chromosome participates in the assembly of virus particles, even though this host protein was not a component of the final virus particles. (e.g.: GroE talk about it latter )

Binding protein (Bip) promote protein assemble B. In plant, a similar assembly-promoting protein in chloroplast was found in pea plant Rubisco is composed of 16 subunits: 8 large subunits and 8 small subunits. And the assembly- promoting proteins are bind to large subunit

C. In mammal, there are also some proteins which binds to the heavy chain that will assist the assembly of multisubunit proteins but is not found in final complex. Binding protein (Bip) promote protein assembly D. Binding protein(Bip): the protein associate with newly synthesized heavy chain.and it can promote protein assembly.

Molecular chaperone Temperature sensitive protein: 1.Sensitive to temperature 2.Small rise in temperature causing this delicate molecule to unfold 3.Under heat shock, soluble protein became denatured and aggregated Molecular chaperone: Temperature goes up Molecular chaperone synthesize Bind to aggregated protein Promote disaggregation Function: assist the assembly of proteins by preventing undesirable interaction and assist polypeptide chain folding.

Classification of molecular chaperone: Example Molecular chaperone Hsp 90 Hsp 70: Bip Hsp 60: GroE sHsp

Hsp best understood chaperone Use GroE as an example: GroE is composed of 2 separate proteins GroEl and Gro ES A model of GroEL: Data from electron microscope 14 polypeptide subunits arranged in 2 stacked rings resembling a double doughnut Reconstruction of GroEl based on High-resolution electron microscope A B GroEL GroES bind toGroEl Central cavity

Hsp best understood chaperone The binding of GroES to GroEL will lead to comformation changes The binding of GroES cap is accompanied by a 60º rotation of apical domain 60º

Hsp best understood chaperone Nonnative polypeptide enter and bind to the hydrophobic site of GroEl Binding of GroES cap produce conformational changes and release of polypeptide. The GroES dissociate Native polypeptide is ejected. Misfold ones rebind to GroEl chamber.

Hsp best understood chaperone How it is possible for a chaperone to bind so many different polypeptide? The binding site has structural flexibility that allows it to adjust its shape to fit the shape of the particular polypeptide with which it has to interact.

Conclusion: Molecular chaperones do not convey information for the folding process but instead prevent proteins from veering off their correct folding pathway and finding themselves in misfolded or aggregated states.