Protein folding

protein structure, function , properties,examples,folding,chaprons,prions,disease examples

1. SOFTVISION COLLEGE,INDORE Department of Bio-Sciences 2018-19 Presentator - Lubaina Kaba Sarvesh Seth Msc .

2. PROTEINS

3. STRUCTURES OF PROTEIN

4. DEFINITION It is referred as any class of complex organic nitrogenous substance found in the cell of living being. They are MACRO-MOLECULES. First described -  Dutch chemist   Gerardus J ohannes Mulder. Named -Swedish chemist  Jons Jacob Berzelius (   1838)

5. AMINO ACIDS A simple organic compound containing TWO functional groups – amino and carboxyl.

6. Formation of peptides

7. STRUCTURE OF PROTEINS Primary Structure Secondary Structure Tertiary Structure Quaternary Structure

8. PRIMARY STRUCTURE They are linear sequence of amino acids.

9. SECONDARY STRUCTURE The conformation of polypeptide chain by twisting or folding. They are two types- A lpha helix . B eta sheet.

10. Alpha-Helix Proposed by –PAULING and COREY(1951). They tightly packed coiled structure. It is stabilized by intra molecular H-bond. Lowest energy.

11. BETA-SHEET They have parallel alignment. They are second type of secondary structure, minimum energy . They depend on intermolecular H-bond.

12. TERTIARY STRUCTURE It is a globular protein consisting of small helix. It is a compact structure. It has different other bonds besides hydrogen, like disulfide bond ,ionic interaction.

13. QUATERNARY STRUCTURE It is the arrangement of more than one  protein  molecule in a multi-subunit complex.  Protein consisting of two or more polypeptides are also termed as OLIGOMERS.

14. FUNCTIONS 1. They serve as body building units, e.g., muscle proteins. 2. They provide support and protection to various tissues, e.g., collagen and keratin. 3. All chemical reactions in the body are catalysed by enzymes, e.g., trypsin. 4. They transport various molecules and ions from one organ to the other, e.g., hemoglobin, serum albumin. 5. They store and provide nutrients, e.g., milk casein,. 6. They defend the body from harmful foreign organisms, e.g., immunoglobulin’s, fibrinogen. 7. They help to regulate cellular or physiological activity, e.g., hormones, viz., insulin, GH.

15. PROPERTIES 1. Denaturation: Partial or complete unfolding of the native (natural) conformation of the polypeptide chain is known as denaturation. This is caused by heat, acids, alkalies, alcohol, acetone, urea, beta- mercaptoethanol. 2. Coagulation: When proteins are denatured by heat, they form insoluble aggregates known as coagulum. All the proteins are not heat coagulable, only a few like the albumins, globulins are heat coagulable.

16. 3.Isoelectric pH (pH 1 ): The pH at which a protein has equal number of positive and negative charges is known as isoelectric pH. When subjected to an electric field the proteins do not move either towards anode or cathode, hence this property is used to isolate proteins

17. MYOGLOBIN Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue . Myoglobin is the primary oxygen-carrying pigment of muscle tissues. Myoglobin is composed of a single polypeptide chain of 153 amino acid residues.

18. HEMOGLOBIN Hemoglobin  is a protein in your red blood cells that carries oxygen to your body's organs and tissues and transports carbon dioxide from your organs and tissues back to your lungs.

19. STRUCTURE OF HAEMOGLOBIN Iron containing pigment called Haem attached with protein – Globin . Haeme is Iron – porphyrin complex called IRON- PROTOPORPHYRIN . Globin – Protein.

20. Protein Folding

21. Nascent P rotein Native Protein Protein folding  is the process by which a  protein structure assumes its functional shape or conformation. All protein molecules are heterogeneous unbranched chains of amino acids. By coiling and folding into a specific three-dimensional shape they are able to perform their biological function.

22. The Central Dogma

23. Co-translational protein folding Protein folding C-terminal N-terminal

24. Mechanism

25. Non-Polar Polar Final conformation of the protein is coded in linear amino acid sequence. Due to Intra molecular H bonding between H of amide group and O of carboxyl group these linear structures form 3-D non functional structures. These structure may form either an alpha helix or beta pleated structures.

26. Extensive intra molecular H bond are present in Beta pleated structure. &

27. These molecules are AMPHIPATHIC in nature .

28. Hydrophobic Hydrophilic This structure is responsible for the function of the Protein. If the Protein Folding doesn’t occur It becomes Non-functional & may cause lethal Disease. (Polar) (Non polar)

29. Multiple Polypeptide of Tertiary Structures assemble to give Quaternary Structure. An example of Quaternary Structure is Hemoglobin Molecule.

30. Chaperons They are group of proteins that provides assistance to the proteins. They keep the protein on right path during folding. HSP proteins and Chaperonins are class of molecules that assist Protein Folding. Several heat shock proteins function as intra-cellular  chaperones  for other proteins. They play an important role in establishment of proper protein  conformation  (shape) and prevention of unwanted protein aggregation.

31. Assistance of enzymes Protein Disulphide Isomerase (pdi) Peptidyl prolyl isomerase (ppi) Pdi promotes the formation and stability of Disulphide bonds between Cysteine residues. PPI Interconvert the cis and trans isomers of peptide bonds with the amino acid Prolin .

32. Role of chaprehones Proteases Proteolysis

33. prions Prions are Proteinaceous Infectious Particles which acts like Virus but is never a Virus. PRNP Is a gene on Chromosome No.20 that Encodes for Prion Protein. Prion protein Represented as prp c Is the normal cellular Prion Protein. It is found on the surface of cells, Neurons (used during Synapses). Prion Represented as PRP sc Is the misfolded protein Where sc represent its Scrapie Form.

34. Prion Proteins are Protease Resistant.

35. why???? Prp c (Normal Folded) Alpha Helix :- 43% Beta Plated Sheets :- 3% Prp sc (Misfolded) Alpha Helix :- 30% Beta Plated Sheets :- 43%

36. Proteopathy Proteopathy refers to the class of Disease which occurs due to Misfolding of Proteins, Some of it’s diseases are KURU, SCRAPIE DISEASE & ALZIEMERS’S DISEASE. KURU is a neurodegenerative disorder which leads to Tremors, loss of co-ordination etc. SCRAPIE is a fatal, degenerative disease that affects the nervous system of Sheeps .

37. SPONGIFORM ENCEPHALOPATHY It is a Brain Tissue degenerative Disorder. In this disorder Healthy tissues of Brain is replaced by cluster of cells which are filled with tiny Liquid Cavities known as Cyst. MAD COW DISEASE (Human Variant)

38. ALZHEIMER’S DISEASE

39. Tau Proteins are the main cause of Alzheimer's disease. Amyloid formation are also one of the causes of this disease.

40. conclusion Protein Folding is an Important Phenomenon of all the Biological Process. Misfolding of Proteins cause lethal diseases. Almost all the disease caused by Protein misfolding are incurable. Protein misfolding  is a common and intrinsic propensity of  proteins  that  occurs continuously

41. Misfolding   Is influenced by the amino acid composition, and certain mutations are known to accelerate the process. Certain Researches are going on misfoldings and disease caused by it. But There is no sufficient cure available for these disease.

42. THANK YOU.