Proteins

• Proteins are biological polymers composed of amino acids.
• Amino acids linked together by peptide bond to form a polypeptide chain.
• One or more polypeptide chain twisted into 3D shape to form protein.
• Protein complex shapes includes various folds, loops and curves.
• It is an essential constituent of all cells.
• It is in every part of body, skin, muscles, hair, blood, organs, eyes, finger nails and bones.
• These are macromolecular polymers composed of amino acid as basic unit.

• Protein molecules: fibrous: elongated and insoluble. And Globular: compact, soluble, spherical.

Globular protein	Fibrous protein
Polypeptide chains are compactly folded to form spherical or globular shape	Polypeptide chains are extended along one axis and are spherically wound to form fibers
4 types of bonds: H-bonds, ionic bonds, disulphide bonds and hydrophobic bonds, which maintains a tertiary structure.	H-bonds between amino acids residue, so usually have high degree of secondary structure.
Soluble in water	Insoluble in water
Non-contractile	Contractile
Ex. Egg albumin, globulins, Hb, all enzymes, etc.	Ex. Alpha-keratin of hair, nails, claws, horns, etc. Elastin, Collagen
	Long, parallel chains form fibres

Types of protein:

Simple protein:

Gives only amino acid on hydrolysis. Ex. Ribonuclease

Composed of only alpha-amino acids.

1. Albumins: soluble in water and dilute in salt solution. It is present in egg white portion and in blood. It is neutral.
2. Globulins: insoluble in water but soluble in dilute salt solution. It is present in antibodies in blood serum and as blood fibrinogen. It is neutral.
3. Histones: soluble in water and insoluble in dilute ammonium hydroxide. It is basic in nature. Ex. Chromatin.

Conjugated protein:

Gives amino acid and non- amino acids components on hydrolysis.

Conjugated proteins:

Class	Prosthetic group	Examples
Lipoprotein	Lipids	Beta1- lipoprotein of blood, yolk, serum, milk, and cell membranes
Glycoprotein	Carbohydrate	Immunoglobulin G
Phosphoprotein	Phosphate group	Casein of milk
Hemoprotein	Heme (Fe porphyrin)	Haemoglobin
Flavoprotein	Flavin nucleotide	Succinate dehydrogenase
Metalloprotein	Fe Zn Ca   Mo Cu	Ferritin Alcohol dehydrogenase Calmodulin (any Ca-bindingg protein) Dinitrogenase Plastocyanin

• Prosthetic group: an inorganic/organic component (non amino acid) that is covalently bound to a protein and essential for its activity.
• Co–factor: an inorganic/organic component is not covalently bound to a protein.

Functional diversity of proteins:

• Enzymes: Hexokinase, kinase, etc.
• Transport proteins: haemoglobin, lipoprotein, membrane transport proteins.
• Nutrient and storage proteins: albumin, casein.
• Contractile protein: actin, myosin, tubulin, etc.
• Structural protein: collagen, desmosine, elastin, keratin, spider web protein.
• Defense protein: immunoglobulin, fibrinogen, thrombin, snake venom, bacterial toxins, rcin, abrin, etc.
• Regulatory protein: hormones, GTP – binding protein.
• Other proteins – antifreeze protein, monellin, etc.

Homologous proteins

Group of protein perform same function in all organism but are evolutionary related (structural resemble)

Example: Hb – oxygen transport

                  Mb – tissues O₂  – transport

                 Cytochrome – C

Conservative substitution:

When one amino acid of one part is changed by another. Ex: 1 polar acid changed by 1 another polar amino acid.

Ubiquitin

With help of ubiquitin, protein degrade after the completion of its function, if ubiquitin do not function then a cell gets block.

Protein conformation

It is stabilized by weak interactions and the stability of unfold state of protein is maintained by high degree of entropy and H-bonding interaction of many group in polypeptide chain.

Conformation:

Spatial arrangement of atoms in a protein and a change in conformation could occur by rotation about single bond.

Levels of architecture of proteins:

• Primary structure: it refers to amino acid sequence and all covalent bond between amino acids and location of disulphide bonds.
• Secondary structure: refers to regular recurring arrangement.
• Tertiary structure: refers to spatial relationship between all amino acids.
• Quaternary structure: refers too spatial relationship between different polypeptides.

Primary structure

It is sequence of amino acids in polypeptide chain.

Unique order in which amino acids are linked together to form a protein.

There is the peptide linkage in the form of bonding.

Structure of peptides are: amino acids whose amino group is free and group called N-terminal end, and other whose carboxyl group is free and group called C-terminal end.

Proteins are constructed from a set of 20 amino acids. Generally, amino acids have following structural properties:

C (alpha-C) bonded to 4 group below:-

• H – atom
• -NH₂ group
• -COOH group
• Variable or R group

Amino acids sequence of a protein is determined by information found in a cellular genetic code.

Secondary structure

Formed by folding of primary structure.

2 polypeptide are held together by H-bonds.

The coiling or folding of a polypeptide chain that gives proteins its 3D structure.

It is the arrangement od amino acids chain due to the H-bonds between atoms at different parts of the chain.

Ex: collagen and silk – fibrin

Proteins can assume 2 conformational structure: α-helix and β-pleated sheet

α-helix:

• Resembles a coiling spring
• Secured by H-bonding in polypeptide chain.
• Constraints which affect the stability of α-helix:
• Electrostatic repulsions (or attraction) between amino acid residues with charged R-group.
• The bulkiness of adjacent R-group.
• The interaction between amino acid side chain spaced 3 or 4 residues apart.
• Occurrence of proline structure.
• Interaction between amino acid at ends of helix and electric dipole inherent to this structure.
• There is intrachain H-bonding.

Β-pleated sheet:

• Appears to be folded or pleated and is held together by H-bonding between polypeptide units of the folded chain that lie adjacent to one another.
• 2 types:
•  Parallel beta sheets:-chains of polypeptides, which run in the same direction.
•  Anti-parallel beta sheets:-chains of polypeptides, which run in the opposite direction to eachother.
•  These are both intra and inter- chain H bonding, it is extended or zig-zag conformations.

Α-helix	Β– helix
Helical conformation	Zig-Zag conformation
Interchain	Inter and Intra- chain
R-group project outside	R-group is projected alternately

Tertiary structure

• Refers to the 3D-structure of polypeptide chains of a protein.
• There are several types of bonds and forces that hold a protein in its tertiary structure.
• Hydrophobic interactions: Greatly contribute to folding and shaping of a protein. ‘R’ group – amino acid: hydrophobic or hydrophilic.
• Hydrophilic R-group: seek contact with aqueous environment
• Hydrophobic R-group: seek to avoid water and position themselves towards the center of protein.
• Hydrogen bonding: In the polypeptide chain and between amino acid R group helps to stabilize protein structure by holding the protein in shape established by hydrophobic interactions.
• Due to protein folding, Ionic bonding can occur between positively and negatively charged R group that come in close contact with one another.
• Folding also results in Covalent bonding between R group of cysteine amino acid. This type of bonding forms: disulfide bridge.
• Interactions called Vander wall forces also assist in stabilization. These contribute to bonding that occurs between molecules.

Quaternary  structure

• Proteins are formed by more than one polypeptide chain and joined together by covalent bond.
• Each polypeptide is called as a subunit.
• Quaternary structure formed by interachain.
• When protein formed by similar subunit : homogenous quaternary structure, and when protein formed by dissimilar subunit: heterogenous quaternary structure. It is consists of 2 identical α-chain and 2- identical β-promoter.
• Most stable structure.

Stability

Less stable to more stable:

Primary to secondary to tertiary to quaternary

Chemical bonds involved in protein structure

1. Strong bonds
2. Peptide bonds: covalent bonds formed by dehydration synthesis between alpha-carboxyl group of one amino acid and alpha-amino group of adjacent amino acid.
3. Disulphide bonds: covalent bonds formed between the S-containing cysteine residue of polypeptide chain.
4. Weak bonds
5. Hydrogen bonds: sharing of H-atoms between the –N and –C=O of different peptide bond.
6. Hydrophobic bonds: when two chains of amino acids come together, no true bonds are formed.
7. Ionic, electrostatic or salt linkages: formed between closely lying –COO and –NH₃ group of different amino group residues.