Molecular chaperones

CHEPERONES

1. CHAPERONES ANJU ANTHARJANAM V.S. DEPARTMENT OF BIOCHEMISTRY UNIVERSITY OF KERALA KARIAVATTOM CAMPUS

2. INTRODUCTION The three dimensional conformation of proteins is important for their biological functions. so how polypeptide chains ultimately fold into their final conformation is also an important topic. Some of the proteins can spontaneously generate the correct functionally active conformation. However a vast majority of proteins can attain correct conformation only through the assistance of certain proteins referred to as chaperones . 2 avs

3. CHAPERONES Chaperones are proteins that interact with unfolded, partially folded or improperly folded polypeptides facilitating correct folding pathways or providing microenvironments in which folding can occur. The chaperones are evolutionary conserved.They are found in all organisms from bacteria to humans and some are homologs with high sequence similarity that use almost identical mechanisms to assist protein folding. Chaperones have ATPase activity ( binding,hydrolysis and exchange of ATP essential for their function). 3 avs

4. Types of chaperones 4 avs

5. Some chaperone homologs and their location Hsp 60 (chaperone 60 family) GroEL in bacterial cytosol Hsp 60 in mitochondrial matrix RubisCo binding protein in chloroplasts Hsp 70(stress70) proteins Hsp 70 in mammalian cytosol Bip in ER of eukaryotes Grp 75 in mitochondria DnaK in bacterial cytosol Hsp 90(stress 90) proteins Hsp 83 in eukaryotic cytosol Grp 94 in mammalian ER Htgp in bacterial cytosol avs 5

6. Molecular chaperones Hsp 70 & Hsp 90 They bind to a short segment of a protein substrate and stabilize unfolded or partly folded proteins thereby preventing these proteins from aggregating and being degraded. Hsp 70 family The heat shock protein Hsp 70 ( Hsp -heat shock protein,70-ml.wt-70,000)and its homologs are the major chaperones in all organisms. They were first identified by their rapid appearance after a cell has been stressed by heat shock. 6 avs

7. Molecular chaperones cntd .. Hsp 70 proteins bind to regions of unfolded polypeptides that are rich in hydrophobic residues,preventing inappropriate aggregation. Hsp 70 proteins also block the folding of certain proteins that must remain unfolded until they have been translocated across a membrane. 7 avs

8. The Hsp 70 proteins bind to and release polypeptides in a cycle that uses energy from ATP hydrolysis and involves several other co-chaperones. Co-chaperones Hsp 40 in eukaryotes and DnaJ in bacteria help to increase efficiency of Hsp 70 mediated folding of many proteins by stimulating substrate binding and hydrolysis of ATP. Other examples are GrpE (in bacteria), BAG,HspBP and Hsp 110(in eukaryotes). 8 avs

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10. Hsp 90 family They are present in all organisms except archaea . They ensure the activation and functional regulation of of their substrates usually called ‘clients’. Hsp 90 function as a dimer in a cycle in which ATP binding , hydrolysis,and ADP release are coupled to conformational changes and to binding,activation,and release of clients. Hsp 90s can help cells recognize misfolded proteins that are unable to refold and facilitate their degradation. 10 avs

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12. CHAPERONINS They form small folding chambers into which all or part of an unfolded protein can be sequestered giving it time and an appropriate environment to fold properly. They are also called Hsp 60s. They are huge cylindrical supramolecular assemblies formed from two rings of oligomers . There are two distinct groups of chaperonins -Group 1 and Group 2 that differ in their structures,molecular mechanism and locations. 12 avs

13. Two classes of chaperonins: Group 1 Found in prokaryotes, chloroplasts and mitochondria. Composed of two rings, each having seven subunits that interact with a homoheptameric co-chaperone lid. GroEL / GroES in bacteria. Group 2 Found in the cytosol of eukaryotic cells and in archaea . Can have 8 to 9 either homo- or hetero- meric subunits in each ring. Lid function is incorporated in ring subunits themselves-no separate lid. ATP hydrolysis triggers the closing of the lid portion. TriC in mammals. 13 avs

14. Structure of GroEL/ GroES system 14 avs

15. Chaperonin in protein folding- 15 avs

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17. REFERENCES Text Book Of Molecular Cell Biology ,7 th Edition,by Arnold Berk , Harvey Lodish Et.Al.,Macmillan . Lehninger Principles Of Biochemistry ,5 th Edition,Michael M.Cox And David L.Nelson . Textbook Of Biochemistry,4 th Edition,U.Sathyanarayana And U.Chakrapani . Hsp 70 Chaperones:cellular Functions And Molecular Mechanism,M.P.Mayer And B.Bukau 17 avs

18. Thank you… 18 avs