Proteins

1. Proteins Proteins, from the Greek proteios, meaning first, are a class of organic compounds which are present in and vital to every living cell. In the form of skin, hair, callus, cartilage, muscles, tendons and ligaments, proteins hold together, protect, and provide structure to the body of a multicelled organism. In the form of enzymes, hormones, antibodies, and globulins, they catalyze, regulate, and protect the body chemistry. In the form of hemoglobin, myoglobin and various lipoproteins, they effect the transport of oxygen and other substances within an organism.

2. Proteins Despite the variety of their physiological function and differences in physical properties--silk is a flexible fiber, horn a tough rigid solid, and the enzyme pepsin water soluble crystals--proteins are sufficiently similar in molecular structure to warrant treating them as a single chemical family.

3. Types of Proteins Fibrous Proteins� As the name implies, these substances have fibre-like structures, and serve as the chief structural material in various tissues. Corresponding to this structural function, they are relatively insoluble in water and unaffected by moderate changes in temperature and pH. Subgroups within this category include:� � � Collagens & Elastins, the proteins of connective tissues. tendons and ligaments.� � � Keratins, proteins that are major components of skin, hair, feathers and horn.� � � Fibrin, a protein formed when blood clots. Globular Proteins� Members of this class serve regulatory, maintenance and catalytic roles in living organisms. They include hormones, antibodies and enzymes. and either dissolve or form colloidal suspensions in water. Such proteins are generally more sensitive to temperature and pH change than their fibrous counterparts

4. Composition of Proteins Hydrolysis of proteins by boiling aqueous acid or base yields an assortment of small molecules identified as a-aminocarboxylic acids. More than twenty such components have been isolated. Essential amino acids diet components, since they are not synthesized by human metabolic processes.

5. Naturally Occuring Amino Acids

6. Formation of Peptide Bond Amino acids are joined together in proteins by peptide bonds. A peptide bond forms between the carboxyl group of one amino acid (amino acid 1 in the figure below) and the amino group of the adjacent amino acid (amino acid 2).

7. Amino Acid The basic building block of a protein is the amino acid. Components of an amino acid Each amino acid has at least one amine and one acid functional group     

8. Peptides and polypeptides Glycine and alanine can combine together with the elimination of a molecule of water to produce a dipeptide. It is possible for this to happen in one of two different ways - so you might get two different dipeptides.

9. In each case, the linkage shown in blue in the structure of the dipeptide is known as a peptide link.

10. Peptides The linkage shown in blue in the structure of the dipeptide is known as a peptide link. If you joined three amino acids together, you would get a tripeptide. If you joined lots and lots together (as in a protein chain), you get a polypeptide A protein chain will have somewhere in the range of 50 to 2000 amino acid residues.

11. Naming a Peptide By convention, when you are drawing peptide chains, the -NH2 group which hasn't been converted into a peptide link is written at the left-hand end. The unchanged -COOH group is written at the right-hand end. The end of the peptide chain with the -NH2 group is known as the N-terminal, and the end with the -COOH group is the C-terminal.

12. Protein The end of the peptide chain with the -NH2 group is known as the N-terminal, and the end with the -COOH group is the C-terminal. A protein chain (with the N-terminal on the left) will therefore look like this:

13. Different Levels of Protein Structure  Proteins fold in three dimensions. Protein structure is organized hierarchically from so-called primary structure to quaternary structure. Higher-level structures are motifs and domains.

14. Primary Structure The primary structure is the sequence of amino acids in the polypedptide chain.

15. Secondary Structure Secondary structure is a local regulary occuring structure in proteins and is mainly formed through hydrogen bonds between backbone atoms.

16. Alpha-helix Alpha helix is spiral structure consisting of tightly packed, coiled backbone core with side chains of amino acids extending outwards.

17. Beta-sheets Beta sheets are pleated structures Two or more polypeptide chains Can be parallel or antiparallel

18. Tertiary structure Tertiary structure describes the packing of alpha-helices, beta-sheets and random coils with respect to each other on the level of one whole polypeptide chain. Figure shows the tertiary structure of Chain B of Protein Kinase C Interacting Protein

19. Quaternary structure Quaternary structure only exists, if there is more than one polypeptide chain present in a complex protein. Then quaternary structure describes the spatial organization of the chains. Figure shows both, Chain A and Chain B of Protein Kinase C Interacting Protein forming the quaternary structure.

20. Comparision of different levels of Protein Structure

21. Protein Structure - Compared

22. Supersecondary structures A motif in this sense refers to a small specific combination of secondary structural elements. Intermediate to secondary and tertiary structure. They are stable arrangements of several arrangements of several elements of secondary structure and connections between them. The simplest motif with a specific function consists of two alpha-helices joined by a loop region. Two such motifs are (i) a motif specific for DNA binding and (ii)a motif specific for calcium binding

23. Supersecondary structures form Supersecondary Motifs In many globular proteins, the secondary structural motifs of a-helix or �-pleated sheet forming supersecondary motifs.

24. �-a-� Unit Parallel beta-strands are connected by longer regions of chain which cross the beta-sheet and frequently contain alpha-helical segments. This motif is called the beta-alpha-beta motif and is found in most proteins that have a parallel beta-sheet. All three elements of secondary structure interact forming a hydrophobic core.

25. �-Meander

26. Helix-turn-helix The loop regions connecting alpha-helical segments can have important functions. For example, in parvalbumin there is helix-turn-helix motif which appears three times in the structure. Two of these motifs are involved in binding calcium by virtue of carboxyl side chains and main chain carbonyl groups. This motif has been called the EF hand as one is located between the E and F helices of parvalbumin. It now appears to be a ubiquitous calcium binding motif present in several other calcium-sensing proteins such as calmodulin and troponin C.

27. Helix-turn-helix Other examples include the helix-turn-helix domain of bacterial proteins that regulate transcription and the leucine zipper, helix-loop-helix and zinc finger domains of eukaryotic transcriptional regulators.

28. Domains Different regions along a single polypeptide chain can act as independent units, to the extent that they can� be excised from the chain, and still be shown to fold correctly, and often still exhibit biological activity.� These independent regions are termed domains.

29. Domains Domains sometimes act completely independently of each other, as in the case of a catalytic domain and a binding domain, where the two domains don't interact with each other, but their association is synergistically because the linker between them means that the catalytic domain is kept in close contact to its substrate. In this case, the interaction between the domains should be considered as something akin to quaternary structure, rather that treating the whole complex as a single protein.

30. Functions of Domain The tertiary structure of many proteins is built from several domains. Often each domain has a separate function to perform for the protein, such as: binding a small ligand (e.g., a peptide in the molecule shown here) spanning the plasma membrane (transmembrane proteins) containing the catalytic site (enzymes) DNA-binding (in transcription factors) providing a surface to bind specifically to another protein.

31. Functions of Domain

32. Transmembrane proteins The polypeptide chain actually traverses the lipid bilayer. The figure shows a transmembrane protein that passes just once through the bilayer and another that passes through it 7 times. All G-protein receptors (e.g., receptors of peptide hormones)