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1. STRUCTURE OF PROTEIN TERTIARY AND QUATERNARY STRUCTURES

2. AIMEN JAVAID HIRA LIAQAT MAHA NADEEM SIDRA ZAFAR IZZA SADAOZAI ANEESA KHALID IQRA ASLAM FAHAD BIN AFTAB NIMRA MUSHTAQ SANA AFTAB Presented by:

3. The tertiary structure defines the specific overall 3-d shape of the protein. Tertiary structure refers to the folding of domains and the final arrangement of domains in the polypeptide. domain : the basic unit of structure and function It is based on various types of interactions between the side-chains of the peptide chain . TERTIARY STRUCTURE OF GLOBULAR PROTEINS

4. In globular proteins Tertiary interactions are frequently stabilized by sequestration of hydrophobic amino acid residues in the protein core. Consequent enrichment of charged or hydrophilic residues on the protein’s water-exposed surface. In secreted proteins disulfide bonds between cysteine residue helps to maintain the protein’s tertiary structure. Tertiary structure stabilization

5. Disulfide bonds Hydrophobic interactions Hydrogen bonds Ionic interactions Vander Waals force Interactions stabilizing tertiary structure

6. A covalent linkage formed from the sulfhydryl group (-SH) of each of two cysteine residues to produce a cystine residue. The two cysteines may be separated by each other by many amino acid in a primary sequence of a polypeptide or may even located on two different polypeptide chains. The folding of the polypeptide brings the cysteine residues in close proximity and permits covalent bonding of their side chains. Disulfide bond contributes to the stability of three dimensional shape of the protein molecule. It prevents protein from becoming denatured in the extracellular environment. Example : disulfide bonds in “immunoglobulin” Disulfide bonds

7. Normally occur between nonpolar side chains of amino acid. The “R” group of the hydrophobic amino acid aggregate together in the centre away from water, thereby developing a force of attraction between each “R” group and a force of repulsion from the water and these interactions are known as hydrophobic interactions. They constitute the major stabilizing force for tertiary structure forming a compact three-dimensional structure. Hydrophobic interactions

8. Normally formed by t he polar side chains of the amino acids. Amino acid side chains containing oxygen or nitrogen –bound hydrogen can form hydrogen bond with electron-rich atoms such as oxygen of carboxyl group or carbonyl group of a peptide bond. Formation of hydrogen bonds enhances the solubility of the protein. Hydrogen bonds

9. Formed between acidic and basic amino acid groups Negatively charged groups, such as carboxylate group in the side chain of ASPARTATE or GLUTAMATE ,can interact with positively charged group , such as amino group in the side chain of LYSINE. Ionic interactions

10. Vander Waals forces, relatively weak electrical forces that attract neutral molecules to one another in gases, in liquefied and solidified gases, and in almost all organic liquids and solids. Vander Waals forces may arise from three sources. First, the molecules of some materials, although electrically neutral, may be permanent electric dipoles. Second, the presence of molecules that are permanent dipoles. Third , even though no molecules of a material are permanent dipoles ( e.g in the noble gas argon or the organic liquid benzene). Vander Waals forces

11. A domain is a basic structural unit of a protein structure distinct from those that make up the confirmations. Part of protein that can fold into a stable structure independently. Different domain can impart different functions to proteins. Protein can have one to many domains depending on the length of polypeptide chain. The core of the domain is built from combinations of supersecondary structural elements (motifs). Each domain has the characteristics of a small,compact globular protein that is structurally independent of the other domains in the polypeptide chain. DOMAINS

12. After being translated from mRNA, all proteins start out on a ribosome as a linear sequence of amino acids. This linear sequence must “fold” during and after the synthesis so that the protein can acquire what is known as its native conformation. The native conformation of a protein is a stable three-dimensional structure that strongly determines a protein’s biological function. When a protein loses its biological function as a result of a loss of three-dimensional structure, we say that the protein has undergone denaturation. Proteins can be denatured not only by heat, but also by extremes of pH; these two conditions affect the weak interactions and the hydrogen bonds that are responsible for a protein’s three-dimensional structure. Even if a protein is properly specified by its corresponding mRNA, it could take on a completely dysfunctional shape if abnormal temperature or pH conditions prevent it from folding correctly. The denatured state of the protein does not equate with the unfolding of the protein and randomization of conformation. Actually, denatured proteins exist in a set of partially-folded states that are currently poorly understood. Protein folding may be primary secondary tertiary or quaternary depends upon the sequence of amino acid . PROTEIN FOLDING

13. Electric and magnetic field. Temperature. PH. Chemicals Molecular crowding FACTORS AFFECTING FOLDING OF PROTEINS

14. Protein folding is a process in which a linear chain of amino acids attains a defined three-dimensional structure, but there is a possibility of forming misfolded or denatured proteins, which are often inactive. Proteins must also be located in the correct part of the cell in order to function correctly; therefore, a signal sequence is often attached to direct the protein to its proper location, which is removed after it attains its location. PROTEIN FOLDING

15. Protein misfolding is the cause of numerous diseases, such as mad cow disease, Creutzfeldt-Jakob disease, and cystic fibrosis. Folding of a protein begins at the process of translation where amino acids interact together and forms polymers of proteins. Protein folding can be due to its amino acid sequence if amino acid sequence is denatured the protein fold is misfolded . Example; sickle cell anemia.

16. Denaturation , in biological process modifying the molecular structure of a protein. Denaturation involves the breaking of many of the weak linkages, or bonds ( e.g.,  hydrogen bonds), within a protein molecule that are responsible for the highly ordered structure of the protein in its natural (native) state. Denaturation can be brought about in various ways— e.g.,  by heating, by treatment with alkali, acid, urea or detergents, and by vigorous shaking. A common consequence of denaturation is loss of biological activity ( e.g.,  loss of the catalytic ability of an enzyme). The denatured protein has the same primary structure as the original, or native, protein. DENATURATION OF PROTEINS

17. A classic example of denaturing in proteins comes from egg whites, which are typically largely egg albumins in water. Fresh from the eggs, egg whites are transparent and liquid. Cooking the thermally unstable whites turns them opaque, forming an interconnected solid mass. EXAMPLE

18. In quaternary structure denaturation, protein sub-units are dissociated and/or the spatial arrangement of protein subunits is disrupted .   Tertiary structure denaturation involves the disruption of: covalent interactions between amino acid side chains (such as  disulphide bridges  between  cysteine  groups) Non-covalent dipole -dipole interactions between polar amino acid side-chains (and the surrounding solvent) Vaander wall induced dipole interactions between nonpolar amino acid side-chains. How denaturation occurs at levels of protein structure;

19. Information for correct protein folding is contained in primary structure of polypeptide. Mostly, protein after being denatured donot resume their native confirmations even under favorable conditions. Because many protein have a facilitated process of folding, that requires a specialized group of protein known as “ molecular chaperons”. They promote correct folding of substrate protein by unfolding incorrect polypeptide chain conformations. Chaperones also known as heat shock proteins, interact with polypeptide at various stages during folding process ROLE OF CHAPERONES IN PROTEIN FOLDING

20. Some chaperons bind hydrophobic regions of an extended polypeptide. They keep the protein unfolded until its synthesis is completed. Example : hsp70 Some chaperon form cage like structures. The partially folded protein enters the cage, binds the central cavity through hydrophobic interaction, folds and is released. Example : mitochondrial hsp60 They facilitate correct protein folding and prevent premature folding. ROLE OF CHAPERONES IN PROTEIN FOLDING

21. The structure that results from the assembly of several polypeptides that may be structurally identical or totally unrelated to make a unique functional protein is called the quaternary structure of protein. These are stabilized by non-covalent interactions These subunits may either function independently of each other or may work cooperatively such as in hemoglobin. Quaternary structure of protein

22. Two kinds of quaternary structures, both are multi subunit proteins HOMODIMER – Association between identical polypeptide chains. HETERODIMER- Interactions between subunits of different structures. It adds stability by decreasing the surface/volume ratio of smaller subunit. Quaternary structure of protein

23. Amyloidosis is a rare disease that occur when an abnormal protein, called amyloid,builds up I your organ and interferes with their normal function. Amyloid isn’t normally found in the body, but it can be formed from several different types of protein. Organs that may be affected include the heart, kidneys, liver, spleen, nervous system and digestive tract. SYMPTOMS: Symptoms include swelling of your ankles and legs . Severe fatigue and weakness shortness of breath with minimal exertion Unable to lie flat in bed due to shortness of breath Numbness ,tingling or pain in hands or feet, especially pain in wrist(carpel tunnel syndrome) diarrhea , possibly with blood, or constipation AMYLOID

24. Factors that increase your risk of amyloidosis include Age –most people diagnosed with amyloidosis are between 60 and 70, altough earlier onset occurs Sex-occur more commonly in men. Other diseases-having a chronic infectious or inflammatory disease increase the risk of amyloidosis . Family history-some types of amyloidosis are hereditary. Risk factors

25. Prions It is a type of protein that can trigger normal proteins in the brain to fold abnormally. Prion diseases can affect both humans and animals and are sometimes spread to humans by infected meat product. The most common form of prions disease that affects human is Creutzfeldt-Jakob disease (CJD). Prion disease occur due to presence of imbalance amino acids in the structure of amino acid. Prion disease is the assemblage of kuru and many cow disease especially damage the protein of the brain in animal.

26. Symptoms of prions diseases include : Rapidly developing dementia Difficulty walking and change in gait Hallucinations Muscle stifness Confusion Fatigue Difficulty speaking Symptoms

27. Risk factor of prion disease include: Family history of prion disease Eating meat infected by mad cow disease Infection from receiving contaminated corneas from contaminated medical equipment Risk factor

28. REFERENCES Lippincott Harper’s biochemistry MN Chatterjea M u s h t a q A h m a d b i o c h e m istry https://www.slideshare.net/mobile/ArchanaMadpathi/protein-denaturation https://www.slideshare.net/devadevi666/protein-structure-presentation