The relationship between structure and function is evident in proteins, which exhibits diversity of function. The sequence of amino acids produce a strong, fibrous structure found in hair, wool and some protein that transport oxygen in the blood. The amino acids sequence is a form that diverts the folding of the protein into its unique three dimensional structures and ultimately determines the function protein. (Lehinger, 1995).
The sequences of amino acids in a polypeptide chain determine the final three dimensional structure of the protein which ultimately functions for various biological activities in the living organisms.
Hierarchical structures of protein: A protein chain folds into a distinct three dimensional shape that is stabilized by non-covalent interactions between the regions of linear sequences of amino acid and is specified by amino acid sequences. Because the folding of protein is very complex, different elements of structure are considered separately. The structures include primary, secondary, tertiary and the quaternary structures of the proteins.
1. Primary structures of protein: It is just a sequence of amino acids in a polypeptide chain. It is also a linear arrangement of amino acids. It indicates the covalent structures of the protein, sequences of amino acid residues and position of the any interchange links such as disulfide bond. It is a sequence which determines the further level of organization of the protein molecule. To represent the primary structures of the protein, the N-terminus is always written on the left sides and the C-terminus is on the right end of the chain.
A short chain of amino acid linked by peptide bond is referred as oligopeptide and long chain is polypeptide.
2. Secondary structure. It referred to the regular folding of polypeptide chains without reference to the side chains. Polypeptide chains are hold together by the hydrogen bond between amine and carboxyl backbone. A single peptide may contain multiple types of secondary structures in various protein of the chain depending on its structures.
a. Alpha (Î±) helix: it is a cylindrical rod like helical arrangement of the amino acid in the polypeptide chain which is maintained by the hydrogen bond parallel to it. Each turn of the helix contains 3.6 amino acid residues and is 5.4Çº long with a diameter of 6Çº. (Lehninger, A.L 1995)
B. Î²-sheet: in this type the molecules is almost completely extended and hydrogen bonds form between peptide group of polypeptide segments lying adjacent and parallel with one another. The side chain lies alternately above and below the main chain. Two segments of a polypeptide chain can result in the formation of the two types of the Î²-structure which solely depends on the orientation of the segments. In Î²-conformation the backbone of the polypeptide chain is extended into a zigzag rather than the helical structure. The adjacent polypeptide chain in a Î²-sheet can be either parallel or antiparallel. (Lehninger, A.L 1995)
3. Tertiary structure. It is referred to overall folding of the polypeptide chain. The polypeptide may be regular which is maintained by hydrogen bonding. The folding includes secondary structures in such a way to expose polar group to the surface and non-polar groups toward interior. The structure is primarily stabilized by the hydrophobic interactions non-polar side chain together with hydrogen bond between the polar sides’ chain and peptides side chains. (Ottaway, J.H. 1984).
What holds protein into secondary structures? Hydrophobic interaction: In most globular protein half of the amino acids have hydrophobic side chains which are internally clustered in folded protein while hydrophobic polar side chain are external.
Hydrogen bonding: many of the amino acid side chain can form the hydrogen bond which contributes to the protein folding. Since many polar groups are on the surfaces of the protein folded
Ionic bonding: side chains of opposite charge attract each other. The strength of such bonds decreases with increase in the dielectric constant on the surface of the protein, where most ionic groups are situated the dielectric constant is high and the bonding is weak.
Covalent bond: the only type of interchain bond is the disulphide bond is cysteine. Disulphide bond are common in structural protein and in extracellular enzymes.
De-naturation of protein: The three dimensional structures is characteristics of a native proteins. This conformation can be organized without the breakage of any peptide linkage, only by the rupture of the linkages which enable the structure to maintain its conformation in the space. The denaturation of the protein can be triggered by diverse physical and chemical agents such as heat, detergents, organic solvents and PH value. (Weil, 1990)
None of the agents break the peptide bonds, so the primary structure remains contact, when it is denatured. When a protein is denatured it only loses its function. After gently denatured, it returned to the normal condition of temperature, PH, salt concentration, which spontaneously regains it function. So its amino acid sequence ultimately helps in protein structure. Fig: Renaturation (The rules of protein structure)
Diversity of protein structure: While studying the three dimensional conformation of protein. They are of two types:
1) Fibrous protein is also called as scleroprotein. As they indicate by the name fibers, Fibrous protein is invariably insoluble. This includes silk fibrous, collagen found in conjunctive tissues, cartilage, tendon and keratin present in the skin and superficial body growth (hairs, nails, horns, feather etc).
Î±-keratin: the Î±-keratin has evolved mainly to provide strength. The protein in case of the mammals constitutes almost the entire dry weight of hairs, wool, nails, claws and many of the outer layers of the skin. The Î±-keratin is right handed Î±-helixes. Francis and Linnus Pauling in 1950s have suggested that helixes of keratin were arranged in coiled coil. When Î±-keratin is exposed to the moist heat and stretched, it is converted to different conformation form, namely Î²-keratin. The hydrogen bonds stabilizing the Î±-helical structure are broken under these conditions result in the extended parallel Î²-pleated sheet. (Conn, Eric E.1985)
b.Collagen: triple helical structure exhibited by collagen, a protein found in the skin, cartilage and bone which provide strength. Collagen consists of parallel bundle of individual linear fibrils that are highly soluble in water. The amino acid composition of collagen is unusual, being composed of 25% of glycine and 25% of proline and hydroxyproline. Because of this, no Î±-helix occurs. Each linear fibrils is capable of consisting of three polypeptide chains. Each chain is twisted into left handed helix and held by interchain hydrogen bond. (Conn, Erie E. 1985).
Globular protein: is also called as the spheroprotein. On the account of their spherical and ovoid shape. These proteins are easily soluble. This group includes mainly albumins and globulins. (Weil.1990). The albumins which are soluble even in distilled water. The iso-electric point is generally less than that of the 7.hence they are acidic in nature. The globulins which are insoluble in pure water and soluble in dilute saline solutions (eg.5% of NaCL). They are often glycoprotein or lipoprotein.
Myoglobin: is a protein which is unusual in having high contents of Î±-helix, but no Î²-sheet. The nine Î±-helical regions contain are 80% of the amino acid, many of which contain are proline. It is a single chain protein found in muscles fiber, structurally similar to a single subunit of hemoglobin and having higher affinity for oxygen than the hemoglobin in blood. It is oxygen carrying protein in vertebrates which facilitates the transport of oxygen in muscles and serves as the reserve store of oxygen in the tissues. It is a single polypeptide chain of 153 residues which has a compact shape. Internally, non-polar residues are present. Externally both polar and the non-polar residues are present. About 75% of polypeptide chain is Î±-helical. There are 8 helical segments in total. (Stryer,1981)
b.Hamoblobin: the oxygen carrying protein of the blood contains two Î± and two Î² subunits arranged with a quaternary structure in the form Î±2Î²2, hemoglobin is therefore a hetero-oligomeric protein.
References: Conn, E.E,
Mammalian Cells: Structure and Function
Mammalian cells are eukaryotic cells that contain a membrane-bound nucleus and vast sub-cellular compartments called organelles, this structure defines eukaryotic cells and is the significant feature that makes them differ to prokaryotic cells. The organelles within the mammalian cell are the structures required for biological processes, which include making protein and extracting and utilising usable energy from food. This Compartmentation allows incompatible chemical reactions to be separated and therefore react in optimum conditions. The membranes along with the interior spaces of each organelle “contain a unique group of proteins” enabling each structure to carry out a unique function. The main organelles within a eukaryotic cell are the: nucleus, endoplasmic reticulum, Golgi complexes, lysosomes, mitochondria and an internal cytoskeleton.
The plasma membrane surrounds the cytoplasm and separates the cell from its external environment. The internal compartmentation within all eukaryotic cells is also achieved by the membrane surrounding each organelle, which have the same basic phospholipid bilayer as the plasma membrane surrounding the cell. Proteins within the cell membrane are largely responsible for a membrane functional properties due to specific membrane transport proteins it is selectively permeable. Specialised areas of the cell membrane called cell junctions contain proteins, and glycolipids that form specific structures between cells and allow for the exchange of metabolites. Proteins on the cell membrane also act as receptors by binding specific signalling molecules, such as hormones, growth factors and neurotransmitter with are crucial for cell development and their functions. The first model of the fluids mosaic structure of the cell membrane “was put forward by Singer and Nicolson in 1982, and is generally accepted as the most reasonable of models”1. Each compartment’s membrane divides the cell’s cytoplasm into different organelles, in each separate compartment there are specific substrates and enzymes for particular cellular activities. This compartmentation allows different cellular functions to occur specific sites at an increased efficiency. It is vitally important to have these compartments within a cell as it allows vital functions of the cell to occur at specialised settings.
Mammalian cells maintain their shape due to the cytoskeleton which is composed of the microtubules, intermediate filaments and microfilaments within the cytoplasm. These all feature linear structures, which are composed of monomers and represent a flexible system. This is particularly apparent at cell division, when the tubular microtubules polymerise from individual monomers of tubulin and form the spindle, which is the structure to which the chromosomes become attached at mitotic cell division. This is the time when each chromosome divides into two genetically identical daughter chromosomes, with one moving to each pole of the cell. The microtubules of the spindle disassemble after division has occurred, and are recycled back into the cytoplasmic microtubules and tubulin monomers of interphase.
The nucleus contains the majority of the mammalian cell’s genetic material which is organised into long linear DNA molecules, which are associated with proteins such as histones to form chromosomes, however during interphase and prophase the chromosomes are not visible and the chromosomes are indistinguishable and in the form of chromatin. The nucleus is the largest organelle in a mammalian cell, and has a double membrane containing numerous different proteins. The outer nuclear membrane is associated with the rough endoplasmic reticulum, while the inner nuclear membrane defines the nucleus itself. Both membranes appear to fuse at the nuclear pores, which are composed of nucleoporins; the nuclear pores allow material to move between the nucleus and the cytosol. Most of the cells rRNA is synthesised by transcription from DNA within the nucleolus- a organelle contained within the nucleus.. In addition the small and large subunits of ribosomes are assembled in the nucleolus and they leave the nucleus through the nuclear pores and are assembled into complete ribosomes
The endoplasmic reticulum is composed of numerous cisternae lying throughout the cytoplasm. The organelle has many essential functions but most importantly plays a role in the synthesis of lipids, membrane protein and secreted proteins. The smooth endoplasmic reticulum lacks ribosomes, and synthesis of fatty acids and phospholipids. The smooth endoplasmic reticulum is abundant in the liver in hepatocytes; enzymes in this organelle in the liver modify or detoxify hydrophobic chemicals by converting these substances into more water-soluble molecules so they can be excreted from the body. The smooth endoplasmic reticulum appears smooth due to the absence of ribosomes on its structure in comparison to the rough endoplasmic reticulum which is studded with ribosomes and its surface appears ‘rough’ under a microscope. Cytoplasmic ribosomes that are associated with the rough endoplasmic reticulum synthesis particular membrane and all organelle proteins and the majority of proteins all proteins that are then secreted out of the cell. The ribosomes synthesis proteins by using information coding from mRNA which emerges out of the nucleus through the pores in the nuclear envelope, this process of making mRNA from DNA is called transcription and this process occurs within the nucleus. The molecule tRNA is required during protein synthesis to bring amino acids into a linear chain that is coded from mRNA. The rRNA contained within the ribosomes assembles the components together to synthesise a linear protein molecule in a process called translation that takes place within the cytoplasm of the cell. This new protein molecule subsequently folds up in the cisternae in the rough endoplasmic reticulum where it matures and finally folds into a three-dimensional functional form.
The proteins synthesised in the rough endoplasmic reticulum are transported via membranous vesicles to the Golgi apparatus. The Golgi complex is a series of cisternae formed from regions of the rough endoplasmic reticulum. The stacks of the Golgi cisternae has three defined regions, the cis, the medial and the trans, transport vesicles from the rough endoplasmic reticulum fuse with the cis region and deposit their contents, the proteins then process through the other regions of the Golgi complex in order depicted above. Within each region they are modified by different luminal enzymes depending on their structure and final destinations. The proteins are then transported out of the cell via vesicles which bud from the trans-side of the Golgi complex.
Endosomes take up soluble macromolecules from the cell exterior to the Golgi complex where their contents may be utilised or degraded by lysosomes. Lysosomes are spherical bodies they are filled with about fifty different hydrolytic enzymes, in acidic solutions. There function is to digest materials that the cells consume from the environment, for example bacteria engulfed by white blood cells, the bacteria are hydrolyzed by the hydrolytic enzymes from lysosomes, while the useful substances are absorbed into the cytoplasm of the white blood cells and undigested components are removed by exocytosis. In addition they digest parts of the cell or worn out organelles, in a similar way as above, this is called autophagy. In addition they release their enzymes by exocytosis and break down other cells. Mammalian cells also contain peroxisomes which are concentrated in the liver and the kidney. They appear very similar to lysosomes but contain d-amino acid oxidase, catalase and peroxidise, and in addition possess a crystalline internum. They are able to degrade toxic products within to form harmless products. For example they break down hydrogen peroxide that forms when organic substances are oxidised.
Mitochondria occupy twenty-five percent of the cytoplasm and are the main site for aerobic respiration. It is a rod-shaped organelle with a double membrane separated by an inter-membranal space. The outer membrane is composed of lipids and proteins in an approximate ‘fifty-fifty’ ratio, and is more permeable than the inner membrane, which has a large surface area as has many invaginations called cristae. The inner membrane the matrix where the Kreb’s cycle takes place using glucose which has initially been degraded, and then reduced in glycolysis reaction to pyruvate, is broken down into even smaller molecules of acetyl coA which drive the reduction of coenzymes which force protons to become concentrated in the space between inner and outer mitochondrial membranes. Compartmentation is required to accommodate the pH and potential gradients necessary for oxidative phosphorylation. In terms of its evolutionary development, the outer mitochondrial membrane is thought to have arisen from a primitive endocytotic event, when a prokaryotic cell was internalized by a eukaryotic cell and remained as a symbiont, as it is a similar size to a prokaryotic cell and unusually lacks-membrane bound organelles with its structure.
In conclusion mammalian cells have a very complex structure containing internal membrane-bound compartments that are specialised to specific tasks. This structure allows eukaryotic cells to maintain different environments in different sections of each cell, and assists with metabolic control by keeping enzymes, substrates and regulators in separate locations with access between them. Each organelle within the mammalian cell is unique and specialised to perform different functions, and the compartmentation allows the different functions to perform at their optimum conditions and thus allows for many complex life processes to take place within the cell.