Protein Chemistry 2 Final Update - HNU PDF

Faculty of Medicine Academic Year: 2024-2025 Year: 1 Semester: 1 Module: Human Body Function (HBF) 102 Protein classification & structure (protein II) By: Dr. Doaa Saeed Mohamed Lecturer of medical biochemistry & molecular biology Department: Faculty of medici...

Faculty of Medicine Academic Year: 2024-2025 Year: 1 Semester: 1 Module: Human Body Function (HBF) 102 Protein classification & structure (protein II) By: Dr. Doaa Saeed Mohamed Lecturer of medical biochemistry & molecular biology Department: Faculty of medicine, Cairo university 12/9/2024 22  Objectives Identify different types of proteins. Recognize the functional significance of the different types of proteins. Describe the different levels of protein structure. Illustrate protein folding and misfolding. Recognize causes of protein denaturation. Identify effects of protein denaturation. 12/9/2024 HBF - 102 33  Introduction  Proteins involved in almost everything Metabolism Support Transport Regulation Motion 12/9/2024 HBF - 102 44  Introduction Biological importance and function 1- Provide the body with essential amino acids, nitrogen and sulfur. 2- Enzymes are mainly protein in nature. 3- Some hormones are mainly protein in nature (e.g. insulin). 4- The antibodies (immunoglobulins) which play an important role in the body's defensive mechanisms are protein in nature. 5- Hemoglobin is a chromoprotein. It carries O2 from the lung to tissues. 12/9/2024 HBF - 102 55 Classification of proteins 1- Fibrous or structural protein  Keratin- elastin - Collagen  Muscle protein (Myosin and Actin)  Protein of cytoplasm 2- Functional protein or globular proteins Enzymes, Hormones, Receptors, Plasma protein, Hemoglobin 3- Genetic Proteins (DNA-binding proteins) Within Chromosomes, DNA (Genes) are held in complexes with structural Proteins (Histones). 12/9/2024 HBF - 102 6 Building unit of proteins (amino acids) Peptide bonds linking NH2 of one amino acid to COOH of another C–N bond (N terminus – C terminus) dehydration synthesis peptide 12/9/2024 HBF - 102 7 bond Structure of proteins - Proteins in their native state are characterized by their three-dimensional structure. - Proteins which are formed of one polypeptide chain have primary, secondary and tertiary structures. - Proteins which are formed of two or more polypeptide chains have an additional quaternary structure. 12/9/2024 HBF - 102 8 Protein structure & and function Function depends on structure : 3-D structure , twisted, folded, coiled into unique shape pepsin Hemoglobin collagen 12/9/2024 HBF - 102 9 Protein structure Structure of proteins can be divided into 4 orders: 1 - Primary Structure 2 - Secondary structure 3 - Tertiary structure 4 - Quaternary structure 12/9/2024 HBF - 102 10 Protein structure R groups hydrophobic interactions, disulfide bridges, ionic bonds 3° multiple polypeptides hydrophobic 1° interactions aa sequence peptide bonds determined by DNA 2° 4° H bonds 12/9/2024 HBF - 102 11  Primary (1°) Structure  Each polypeptide chain is formed of α-amino acids united by peptide bonds.  Bonds responsible for the maintenance of primary structure are mainly peptide bonds.  The chain starts on the left side by amino acid number 1, which contains a free amino group (N-terminus amino acid).  The chain ends on the right side by the last amino acid with a free carboxylic group (C-terminus amino acid).. 12/9/2024 HBF - 102 12 Primary (1°) Structure  The synthesis of the polypeptide chain starts from the N-terminus and ends toward the C-terminus.  Change of a single amino acid in the polypeptide chain may lead to profound change of physiologic effects.  The genetic information present in DNA controls the 1ry structures of proteins, which determines the secondary and tertiary structures that are essential for functions of proteins. 12/9/2024 HBF - 102 13 Secondary structure (α –Helix & β- sheet) α –Helix (Hydrogen bond in the same chain) It is folding of the polypeptide chain, along its long axis, into specific coiled structure, held together by hydrogen bonds. 12/9/2024 HBF - 102 14 Secondary structure (α –Helix & β- sheet) α-helix may be: Main features of α-helix -The α-helix is stabilized by intra-chain hydrogen bonds formed between NH groups and C=O groups 12/9/2024 HBF - 102 15 Main features of α-helix The R groups of some amino acids can disrupt the -helical structure e.g. proline, tryptophan, histidine, lysine, arginine, aspartic acid and glutamic acid. - This is due to: 1) formation of other types of bonds as ionic bonds. or 2) their ring structures disturb the helical formation. 12/9/2024 HBF - 102 16 Secondary (2°) structure β- sheet Hydrogen bonding between adjacent segments of polypeptide chains. 12/9/2024 HBF - 102 17 Main features of β-pleated sheet  The polypeptide chain is fully extended.  Two or more segments of the polypeptide chain line up side by side to form a sheet, and stabilized by intra-chain hydrogen bonds.  The side chains (R) are above or below the plane of the sheet. 12/9/2024 HBF - 102 18 Main features of β-pleated sheet There are two forms of the β-sheets: 1- Anti-parallel β-pleated sheet: When the adjacent polypeptide chain segments run in opposite direction. 2- Parallel β-pleated sheet: When the adjacent polypeptide chain segments Anti-parallel Parallel strands strands run in same direction (N to C terminus). 12/9/2024 HBF - 102 19 Tertiary (3°) structure It is the folding of the polypeptide chain of a protein into a specific three - dimensional structure forming a globular protein, this structure is maintained by different types of bonds or interactions as: A. Hydrophobic interactions B. Electrostatic bonds C. Hydrogen bonds D. Van der Waals interactions E. Disulfide Bonds 12/9/2024 HBF - 102 20 Tertiary (3°) structure 12/9/2024 HBF - 102 21 Quaternary (4°) structure It is the final and the highest level of protein organization, in which more than one polypeptide chains (subunits or polymers) are linked together (not bonded covalently). Each subunit has its own primary, secondary and tertiary structure Such high level of organization may be essential for the activity of certain proteins e.g. enzymes and hemoglobin. 12/9/2024 HBF - 102 22 Quaternary (4°) structure two or more tertiary folded peptide subunits bonded together to make a functional protein. Ex. Hemoglobin – 4 polypeptides Forces that stabilize the 4ry structure are: -Hydrogen bonding. -Electrostatic interactions. -Hydrophobic interactions. Hemoglobin -Van der Waals interactions. 12/9/2024 HBF - 102 23 -Disulfide bonds. Protein folding Proteins must fold into defined 3D structures to gain functional activity. 12/9/2024 HBF - 102 24 Protein folding To avoid the dangers of abnormal folding and aggregation, a complex network of proteins called “chaperones” use different mechanisms to promote efficient protein folding and prevent aggregation. 12/9/2024 HBF - 102 25 Protein folding An age-related decline in chaperones allows the manifestation of various protein-aggregation diseases, including Alzheimer's disease and Parkinson's disease. 12/9/2024 HBF - 102 26 Denaturation of protein Unfolding a protein/changes the shape  The protein loses its secondary, tertiary & quaternary structures.  By pH change or temperature  disrupts H bonds, ionic bonds & disulfide bridges  destroys functionality. 12/9/2024 HBF - 102 27 Protein denaturation Folding Biologically active 1ry 2ry 3ry 4ry Biologically inactive Not affected 12/9/2024 HBF - 102 28 Denaturation of Proteins Denaturation means unfolding. Causes: Denaturants High temperature, High Strong acids and pressure alkalis, Organic Vigorous shaking, U.V. light, solvents irradiation & exposure to x-ray 12/9/2024 HBF - 102 29  Interactive Question 2ry structure of proteins is stabilized by: a) Ionic bond. b) Hydrophobic interaction. c) Hydrogen bonds. d) Peptide bond. 12/9/2024 HBF - 102 30 30  Interactive Question α-helices and β-pleated sheets are examples of protein's: a.Primary structure. b.Secondary structure. c.Tertiary structure. d.Quaternary structure. 12/9/2024 HBF - 102 31 31  Interactive Question The tertiary structure of proteins is stabilized by the following, except: a. Hydrogen bonds. b. Hydrophobic interactions. c. Peptide bonds. d. Disulfide bonds. 12/9/2024 HBF - 102 32 32  Interactive Question The four-subunit structure of the Hb represents protein's: a. Primary structure. b. Secondary structure. c. Tertiary structure. d. Quaternary structure. 12/9/2024 HBF - 102 33 33  Interactive Question 1ry structure of proteins is stabilized by: a) Ionic bond. b) Hydrophobic interaction. c) Hydrogen bonds. d) Peptide bond. 12/9/2024 HBF - 102 34 34  Interactive Question Enumerate (Mention): - Two bonds that maintain the tertiary structure of proteins. - Three types of forces that hold the tertiary structure of proteins. 12/9/2024 HBF - 102 35 35  Summary Structure of proteins can be divided into 4 orders: 1 - Primary Structure 2 - Secondary structure 3 - Tertiary structure 4 - Quaternary structure Proteins must fold into defined 3D structures to gain functional activity by chaperons 12/9/2024 HBF - 102 36 36  References Lippincott’s Illustrated Reviews: Biochemistry, chapter of protein structure and function. 12/9/2024 HBF - 102 37 37