Amino acids group together to form polypeptide which in turn forms the 3dimesional structures of protein. The 3 dimensional structures of proteins determine the functions for each protein. Proteins are diverse and here I've grouped them in hierarchy of increasing complexity with different examples for each type.
A Compound composed of two or more amino acids is called a peptide and the presence of more than two peptide bonds is called polypeptide. A Polypeptide has different combinations of 20 amino acids which make up enormous number of polypeptides.
Fig. compound showing peptide bond.
Polypeptide formation is due to covalent bond formation. In the peptide the Cï¡ of nearby amino acid residues are separated by 3 covalent bonds, arranged as Cï¡-C-N-Cï¡.
The 6 atoms of the peptide group lie in a single plane, with the oxygen atom of the carbonyl group is in trans to the hydrogen atom of the amide nitrogen. It was concluded that the C-N bonds of peptide are not able to rotate freely because of their double bond whereas rotation is possible about the N-Cï¡ and Cï¡-C bonds.
(Nelson et al, 2001)
The polypeptide chain given rise by sequence of amino acids gives rise to protein structure and the structure formation are on the basis of bonding involved.
(I)Bonds involved:
1) Disulphide bond: Also known as covalent bond which is formed between same or different chains. For example, 2 residues of Cysteine of same/different chains are linked by Covalent bonds.
2) Ionic bonds: Ionic bond is a non-covalent bond formed between positively charged radical and a negatively charged radical joining 2 parts of same/different chains.
3) Hydrogen bonds: This kind of bond is formed when one H atom bonds to a N atom or an O2 atom is in close proximity to one another unshared N or O2 atom.
4) Hydrophobic bond: Some amino acids have a non-polar side chains which does not form any H bond with water molecules; these side chains tend to repel. This repelling force created between different parts of a polypeptide chain is called hydrophobic bond.
(Weil et al, 2008)
3 DIMENSIONAL CONFORMATIONS OF PROTEINS
Peptide linkage gives rise to 4 essential structures in hierarchy:
Fig.3D structure of protein in hierarchy.
(Protein structures (n. d))
MOLECULAR STRUCTURE
Primary (sequence)
Secondary (local folding)
Tertiary (long range folding)
Quaternary(multimeric organization)
(Scott etal,2004).
PROTEIN STRUCTURES IN HIERARCHY
Amino acid sequence specifies the 3D structure of protein and this 3D arrangement derives protein function.
(1)Primary structure.
The linear arrangement of amino acid residues is the primary structure of protein. This amino acid sequence of protein determines the higher levels of structure of the molecule.
(2)Secondary structure.
The second level of protein structure consists of arrangement which results from localized polypeptide chain folding. A single polypeptide has an ability to show numerous kinds of secondary structures.
A polypeptide assumes a random-coil structure due to absence of non-covalent interactions. However sometimes a stabilizing hydrogen bond is formed between residues: the structures like alpha-helix and beta-sheets are formed.
However alpha-helix and beta-sheets are only the internal elements which supports protein and remainder of molecules in a random coil.
(Lodish etal,2004).
(A)The alpha-helix.
The intrachain hydrogen bond keeps the peptide chain in a helicoidal configuration. The angle of 80 degree is formed between the peptide linkages. The side chain of the helix can react with each other or with the medium, since they are directed outward.
The amino acid residues in an alpha-helix have conformation with Phi=-45 degree to -50 degree and Psi=-60 degree and each helical turn has 3.6 amino acid residues.
The formation of several hydrogen-bonds and disulfide bonds is responsible for making the alpha-helix a voluminous and strong fibre.
Fig. Alpha helix.
(alpha helix structures(n.d)
(B)The beta-sheet/Stretched state.
Globular proteins are compact structures and loops or turns these amino acid residues. The common connecting form is the beta-turn that connects the 2 adjacent segment of beta -sheets.
The backbone of the polypeptide chain is extended to form zigzag in the beta conformation.This zigzag polypeptide chain can be arranged side to form a series of plates.
Hydrogen bonds are formed between adjacent segments of polypeptide chain in a beta-sheet. The beta-sheet forming segments are nearby on the polypeptide chain or even be in a different polypeptide chains.
An alternating pattern is formed as a result of R group of amino acids protruding from the zigzag structure in the opposite direction.
The beta-sheet can either be parallel or antiparallel.The parallel or antiparallel form of beta-sheet are somewhat similar,but the repeating unit is longer in antiparallela(7amstrong vs. 6.5amstrong for parallel) and the hydrogen bonding pattern are different from parallel conformation.
The R-groups of the amino acid residue on the touching surfaces must be small when two or more beta-sheets are layered close together in a protein.
(Source:Nelson etal,2001)
A beta-sheet can have a turn composed of 3 or 4 residues, located on the protein surface which forms a bends redirecting the polypeptide backbone towards the inside.
This results in the formation of a U-shaped structure that is stabilized by formation of hydrogen bonds. Glysine and Proline are the best examples of amino acids that forms tightly U-shaped folded protein.
(Lodish etal,2004)
Fig. Parallel beta sheet,
(Protein structures(n.d)
(3)Tertiary and quaternary structures.
Tertiary structures;refers to 3-dimensional arrangement of all its amino acid residues.The tertiary structures are highly stabilized by hydrophobic interactions between non-polar side chains,hydrogen bonds between polar side chains and the peptide bonds.
The secondary structure like alpha-helix and beta-sheets are held by weak fluctuation.
Quaternary structure:Some proteins contains two or more polypeptide chains(subunits),which may be different or identical. The arrangement of this subunits of protein in a 3-dimensional complex is called the quaternary structure.
Globular proteins are the most biologically active proteins and are in more compact form. They consists of several polypeptide chain with variation in their folds and curvature. As the amino acid residues are distant from one another,they can be brought near by folding.
Tertiary and Quaternary structures can be grouped as:
a)Fibrous proteins.
b)Globular proteins.
(Lodish etal,2004)
Fibrous proteins are adapted for a structural function.
(A)Fibrous proteins.
(i)Alpha-keratin.
Alpha-keratin is found in mammals and constitutes the entire weight of hair, wool, nail, claw, horn, hooves and outer layer of skin.
Protein most importantly constitutes the cytoskeleton of an animal cell.
Protein constituting alpha-keratin have a structural features and have a structural function. Oriented in parallel are 2 strands of alpha-keratin and are wrapped to form a coil.
The helical path is left handed compared to the use of right handed alpha-helix. The R-groups of amino acid residues are interlocked permitting a close packing of polypeptide chain.
The quaternary structure of alpha-keratin is more complex. In this alpha-keratin are arranged to assemble the coil into large molecular complex forming intermediate filament of hair.
The fibrous protein has high strength which is due to covalent bond and the quaternary structure strengthened by the disulfide bond formation.
(Nelson etal, 2008)
(ii)Collagen.
Collagen provides strength and is found in tissues such as tendon, cartilage, bone matrix and cornea of eye. It is left handed alpha-helix with distinct tertiary and quaternary structure.
However the twisting is right handed, opposite to left handed helix of alpha chains.
Gelatin, a food product is derived from collagen, the tight conformation of alpha-chain in collagen provides a high tensile strength.
This strength or rigidity is provided by the covalent cross-links in collagen fibrils.
(Nelson etal, 2008)
(iii)Silk fibroin.
Fibroin (protein silk)is a polypeptide chain in more of beta-conformation and is produced by insects and spiders. The fibroin is provided with a great strength due to H bond formation between peptides. However the structure is flexible due to absence of strong bond like covalent ,rather it is held by weak interactions.
(Nelson etal,2001)
(B)Globular protein-Structural diversity reflects functional diversity.
Globular protein has different polypeptide chain folding back on each other. This folding provides the protein, the structural diversity to carry out necessary biological functions. Enzymes, Transport protein, Moter protein, Regulatory protein, immunoglobins belongs to globular protein.
(I)Transport protein.
(i)Myoglobin:Present in muscle tissue of all animals, is a oxygen binding protein called myoglobin.Myoglobin stores oxygen and distributes it to oxygen starved tissues.Myoglobin is composed of 53 amino acid residues and 1 molecule of heme and up to 8 alpha-helical segments, connected by bends.(Nelson etal,200)
Fig.Myoglobin.
(Tertiary protein structures(n.d)
(ii)Hemoglobin.
Hemoglobin carries the oxygen in all animals.Hemoglobin subunits are structurally similar to myoglobin.Myoglobin is insensitive to small changes in oxygen concentration, so functions as oxygen-storage protein. However hemoglobin is better suited for oxygen transport with its many subunits and oxygen binding sites. Hemoglobin types of globins, 2 alpha chains and 2 beta chains.
Oxygen binds to hemoglobin in either R-state/T-state. The binding of oxygen stabilizing the R-state. The oxygen binding to T-state triggers change in conformation to R-state.
This change in conformation is to bind more of oxygen. As a rest of this change in state, hemoglobin has more oxygen binding capacity.
However the oxygen binding capacity in hemoglobin is significantly weaker than that for myoglobin.Inside red cells,hemoglobin interacts with 2,3-biphosphoglycerate,a molecule that significantly lowers homoglobin's oxygen affinity.Also binding reactions at individual sites in each hemoglobin molecule are not independent of each other.
(Nelson etal, 2001)
Fig.hemoglobin
(Tertiary protein structures(n.d)
Hemoglobin also transport H+ and CO2
Apart from carrying oxygen, hemoglobin also carries 2 end products of respiration-H+ and CO2 for excretion. The CO2 is excreted after its hydration to bicarbonate. H+ binds to different site of hemoglobin.O2 binds to heme's iron atom but H+ are bound to H with inverse affinity.
(II)Immunoglobulin.
Immunoglobulin G (igG) has 2 identical antigen binding sites.igG has 2 heavy polypeptide and 2 light polypeptide chains linked by disulfide bond. The heavy chain interacts with light one to form a Y-shaped molecule, which on cleavage on papain liberates basal fragments (FC) and 2 branches (FAB) are the antigen binding fragments.
Fig.Immunoglobulin
(Tertiary protein structures(n.d)
(C)Motor proteins-Actin and Myosin.
Myosin and Actin are 2 of the major proteins of muscle.
1) Myosin-Has 4 heavy sub units and 2 light subunits of which the former 4 accounts for much of overall structure.
At carboxyl terminal, they are extended as alpha-helix while at its amino terminal has globular domain where ATP can be hydrolysed. The aggregate form of myosin called thick filament acts as a contractile unit.
2)Actin-Actin is present in muscle more than myosin and consists of monomer called G-actin and polymer called F-actin.
The monomer binds to form polymer, apart from this monomer also binds ATP,which it hydrolyse to ADP.This ATP hydrolysis indirectly contributes energy for muscle contraction.
The muscle fibre has alternating regions of high and low electron density called A and I bands respectively. The I-band is region of bundle with thin filament and A-band with thick filament.Z disk dissects the I-band and A-band too is dissected by M-disk.This structure with interval of thin and thick filament is called sarcomere.
The thin filament has a protein made up of alpha helix. Another large polypeptide chain called titans links the thick filament to Z-disk.
The actin and myosin interaction between proteins involves weak bonds.ATP not bound to myosin,a face on myosin binds to actin.when ATP binds to myosin,ATP is hydrolysed to ADP+Phosphate,this release F-actin subunit and binds another subunit along the thin filament. This accounts for the muscle-contraction mechanism.
(Nelson etal, 2008)
Fig.Actin,Myosin filament (Kratz,2009)
After writing on the topic mentioned, I can conclude that the structure of proteins are very essential because they determine their specific functions:the way in which
the different chains are bonded together gives the 3 dimensional structure of proteins,which makes it suitable for its function.
