Biological roles of proteins

Proteins play very significant role in cell functioning. they are known as workhorse of cell. they are made up of amino acids.

1. Biological roles of Proteins Course Name : Biochemistry Course Code :BTE-205 Course facilitator: Dr Rajesh Kumar Email : [email protected] Hemoglobin

2. Definition of Proteins Importance of Proteins Protein classification based upon Source of Protein Shape and size Biological role Chemical composition Forces stabilizing Protein structure and shape Different levels of structural organization of Proteins

3. Definition: The proteins are biomolecules, polymeric in nature and known as workhorse in cell. They are made up of twenty amino acids and involved in almost all activities of cell. Transferase enzyme Insulin

4. Importance of Proteins Fundamental basis of cell structure and functions. All the enzymes, cell receptors, transport carriers are proteins. Involved in maintenance of osmotic pressure, blood clotting and muscle contraction. During starvation protein serve as major supplier of energy. Hair and nails are mostly made of protein. Proteins are used to build and repair tissues. Protein is an important building block of bones, muscles, cartilage, skin, and blood. Proteins are required for growth and maintenance of tissue Proteins act as hormones Proteins act as buffer system helping your body to maintain proper pH of blood and other body fluids

5. Protein classifications Based on source Animal protein Plant Proteins Microbial proteins Animal Proteins Plant Proteins

6. Based on structural shape Collagen helix Features of globular protein These have an axial ratio (length : width) of less than 10 (usually not over 3 or 4 ). Possess a relatively spherical or ovoid shape . These are usually soluble in water or in aqueous media containing acids, bases, salts or alcohol, and diffuse readily .

7. Tertiary and quaternary structures are usually associated with this class of proteins . Nearly all enzymes are globular proteins, as are protein hormones, blood transport proteins, antibodies and nutrient storage proteins As a class, globular proteins are more complex in conformation than fibrous proteins, have a far greater variety of biological functions and are dynamic rather than static in their activities.

8. Features of Fibrous or Fibrillar Proteins These have axial ratios greater than 10 and, henceforth, resemble long ribbons or fibres in shape . These are mainly of animal origin and are insoluble in all common solvents such as water, dilute acids, alkalies and salts and also in organic solvents . Most fibrous proteins serve in a structural or protective role.

9. Two main structure-based classification databases, Structural Classification of Proteins (SCOP)) and Class Architecture Topology and Homology (CATH) The focus of SCOP is to structurally characterize the proteins that are deposited in the PDB. SCOP considers evolutionary and structural domains of proteins and classifies them in a hierarchical manner. Classification based upon structure

10. The hierarchy of classification in SCOP database 1.Class (secondary structure composition and sequence/arrangement): members of different folds are placed under same class based on the extent of secondary structural content and order of occurrence of SSEs. Domains in globular proteins are usually classified under the following categories of ‘Class’. a. All α class : members in this class are predominately composed of helices. b. Allßclass : members in this class are predominantly composed of b-sheets. c. α /ß class : members comprise of interspersed helices and b strands in their structure. d. a + b class : members comprise of segregated helices and b strands in their structure. e. Multidomain class : a multidomain class comprises of members with domains of different folds.

11. f. Small proteins : this class includes members corresponding to several disulfide rich and metal binding proteins with few or almost no regular secondary structures. g. Membrane proteins : this class includes membrane proteins. ii. Fold (gross structural similarity): members in different superfamilies are grouped into one fold if the arrangement of major SSEs along with their topological connections is the same. Structural similarity among members in the same fold group arises from physicochemical properties favoring certain packing arrangements and chain topologies.

12. iii. Superfamily (probable evolutionary relationship): families showing overall structural similarity and in many cases gross functional similarity, thus indicating potential common evolutionary origin, are categorized into one Superfamily . iv. Family (clear evolutionary relationship): family can be defined as a collection of related protein regions, which share high sequence identity and usually good functional and structural similarity. Most of the members of a family show more than 30% sequence identity with each other.

13. Protein classification based on Biological functions Enzyme proteins. Examples: Urease, Amylase, Catalase, etc . Structural proteins. Examples: Collagen, Elastin, Fibroin, etc . Transport or carrier proteins. Examples:  Hemoglobin , Lipoproteins Nutrient and storage proteins. Examples: Casein, Ferritin, etc. Contractile or motile proteins. Examples: Actin, Myosin, etc. Defense proteins. Examples: Fibrinogen, Thrombin, etc. Regulatory proteins. Examples: Insulin, G-Proteins, etc. Toxic proteins. Examples: Snake venom, Bacterial toxins, Ricin, etc.

14. Based upon chemical compositions   Simple Proteins or Holoproteins These are of globular type except for scleroproteins which are fibrous in nature. This group includes proteins containing only amino acids, as structural components . On decomposition with acids, these liberate the constituent amino acids. These are further classified mainly on their solubility basis as follows: 1. Protamines and histones 2. Albumins 3. Globulins 4.  Glutelins 5.  Prolamines 6.  Scleroproteins or Albuminoids

15.   Conjugated or Complex Proteins or Heteroproteins These are also of globular type except for the pigment in chicken feathers which is probably of fibrous nature. These are the proteins linked with a separable nonprotein portion called prosthetic group . The prosthetic group may be either a metal or a compound. On decomposition with acids, these liberate the constituent amino acids as well as the prosthetic group. Their further classification is based on the nature of the prosthetic group present. The various divisions are: 1. Metalloproteins 2. Chromoproteins 3. Glycoproteins 4. Phosphoproteins 5. Lipoproteins 6. Nucleoproteins

16.   Derived Proteins These are derivatives of proteins resulting from the action of heat, enzymes or chemical reagents. This group also includes the artificially-produced polypeptides. Derived proteins These are derivatives of proteins in which the size of protein molecule is not altered materially. 1. Proteans : Insoluble in water; appear as first product produced by the action of acids, enzymes or water on proteins. e.g., edestan derived from edestin and myosan derived from myosin. 2. Metaproteins or Infraproteins : Insoluble in water but soluble in dilute acids or alkalies ; produced by further action of acid or alkali on proteins at about 30–60°C. e.g., acid and alkali metaproteins . 3. Coagulated Proteins : Insoluble in water; produced by the action of heat or alcohol on proteins. e.g., coagulated eggwhite .

17. Forces stabilizing protein structure and shape Covalent Bonds Peptide Bond Disulphide Bond Non covalent Bonds Hydrogen Bonds Van der Waals forces Hydrophobic interactions Short range repulsion Electrostatic Bonds

18. Non covalent Bonds A hydrogen bond is a partial intermolecular bonding interaction between a lone pair on an electron rich donor atom, particularly the second-row elements nitrogen, oxygen, or fluorine, and the antibonding molecular orbital of a bond between hydrogen and a more electronegative atom or group Van der Waals forces include attraction and repulsions between atoms, molecules, and surfaces, as well as other intermolecular forces. They differ from covalent and ionic bonding in that they are caused by correlations in the fluctuating polarizations of nearby particles Hydrophobic interactions describe the relations between water and hydrophobes (low water-soluble molecules). Hydrophobes are nonpolar molecules and usually have a long chain of carbons that do not interact with water molecules.

19. When two atoms are close together the occupied orbitals on the atom surfaces overlap, causing electrostatic repulsion between surface electrons. This repulsive force between atoms acts over a very short range, but is very large when distances are short. Short range repulsion Electrostatic Bonds a chemical bond in which one atom loses an electron to form a positive ion and the other atom gains an electron to form a negative ion .

20. Domain: A  protein domain  is a region of the protein's  polypeptide chain  that is self-stabilizing and that folds independently from the rest. Each domain forms a compact  folded  three-dimensional structure. Many proteins consist of several domains. One domain may appear in a variety of different proteins.  Molecular evolution uses domains as building blocks and these may be recombined in different arrangements to create  proteins  with different functions. In general, domains vary in length from between about 50  aa  up to 250 amino acids in length . [  The shortest domains, such as zinc fingers , are stabilized by metal ions or disulfide bridges. Domains often form functional units, such as the calcium-binding EF hand domain of  calmodulin . Because they are independently stable, domains can be "swapped" by genetic engineering between one protein and another to make  chimeric proteins.

21. Pyruvate Kinase : A protein with three domains The concept of the  domain  was first proposed in 1973 by Wetlaufer after X-ray crystallographic studies of hen  lysozyme [2]  and  papain [3]  and by limited proteolysis studies of  immunoglobulins . [4] [5]   Wetlaufer defined domains as stable units of  protein structure  that could fold autonomously

22. Motif: It can be either sequence or structure motif. Sequence motifs have recognizable amino-acid sequences found in different proteins. Structural motifs are segments of protein 3D structure that is formed by the spatially close residues. These residues may or may not be adjacent in the sequence. Zinc finger structural motief

23. Different levels of structural organizations in Proteins Primary structure The simplest level of protein structure, primary structure, is simply the sequence of amino acids in a polypeptide chain . Secondary structure The next level of protein structure, secondary structure, refers to local folded structures that form within a polypeptide due to interactions between atoms of the backbone. (The backbone just refers to the polypeptide chain apart from the R groups –secondary structure does not involve R group atoms .) The most common types of secondary structures are the α helix and the β pleated sheet. Both structures are held in shape by hydrogen bonds, which form between the carbonyl O of one amino acid and the amino H of another.

24. Image credit: OpenStax Biology. In an α helix, the carbonyl (C=O) of one amino acid is hydrogen bonded to the amino H (N-H) of an amino acid that is four down the chain. (E.g., the carbonyl of amino acid 1 would form a hydrogen bond to the N-H of amino acid 5.) This pattern of bonding pulls the polypeptide chain into a helical structure that resembles a curled ribbon, with each turn of the helix containing 3.6 amino acids. The R groups of the amino acids stick outward from the α helix, where they are free to interact. In a β pleated sheet, two or more segments of a polypeptide chain line up next to each other, forming a sheet-like structure held together by hydrogen bonds. The hydrogen bonds form between carbonyl and amino groups of backbone, while the R groups extend above and below the plane of the sheet. The strands of a β pleated sheet may be parallel, pointing in the same direction (meaning that their N- and C-termini match up), or antiparallel, pointing in opposite directions (meaning that the N-terminus of one strand is positioned next to the C-terminus of the other).

25. Tertiary structure The overall three-dimensional structure of a polypeptide is called its tertiary structure. The tertiary structure is primarily due to interactions between the R groups of the amino acids that make up the protein. R group interactions that contribute to tertiary structure include hydrogen bonding, ionic bonding, dipole-dipole interactions, and London dispersion forces – basically, the whole gamut of non-covalent bonds

26. Quaternary structure Many proteins are made up of a single polypeptide chain and have only three levels of structure. However, some proteins are made up of multiple polypeptide chains, also known as subunits. When these subunits come together, they give the protein its quaternary structure. In general, the same types of interactions that contribute to tertiary structure also hold the subunits together to give quaternary structure.

27. Stay safe stay healthy Thanks a lot