Globular proteins or spheroproteins are spherical proteins and are one of the common protein types. Globular proteins are somewhat water-soluble, unlike the fibrous or membrane proteins. There are multiple fold classes of globular proteins, since there are many different architectures that can fold into a spherical shape; the term globin can refer more to proteins including the globin fold. The term globular protein is quite old and is now somewhat archaic given the hundreds of thousands of proteins and more elegant and descriptive structural motif vocabulary; the globular nature of these proteins can be determined without the means of modern techniques, but only by using ultracentrifuges or dynamic light scattering techniques. The spherical structure is induced by the protein's tertiary structure; the molecule's apolar amino acids are bounded towards the molecule's interior whereas polar amino acids are bound outwards, allowing dipole-dipole interactions with the solvent, which explains the molecule's solubility.
Globular proteins are only marginally stable because the free energy released when the protein folded into its native conformation is small. This is; as a primary sequence of a polypeptide chain can form numerous conformations, native globular structure restricts its conformation to a few only. It results in a decrease in randomness, although non-covalent interactions such as hydrophobic interactions stabilize the structure. Although it is still unknown how proteins fold up new evidence has helped advance understanding. Part of the protein folding problem is that several non-covalent, weak interactions are formed, such as hydrogen bonds and Van der Waals interactions. Via several techniques, the mechanism of protein folding is being studied. In the protein’s denatured state, it can be folded into the correct structure. Globular proteins seem to have two mechanisms for protein folding, either the diffusion-collision model or nucleation condensation model, although recent findings have shown globular proteins, such as PTP-BL PDZ2, that fold with characteristic features of both models.
These new findings have shown. The folding of globular proteins has recently been connected to treatment of diseases, anti-cancer ligands have been developed which bind to the folded but not the natural protein; these studies have shown. By the second law of thermodynamics, the free energy difference between unfolded and folded states is contributed by enthalpy and entropy changes; as the free energy difference in a globular protein that results from folding into its native conformation is small, it is marginally stable, thus providing a rapid turnover rate and effective control of protein degradation and synthesis. Unlike fibrous proteins which only play a structural function, globular proteins can act as: Enzymes, by catalyzing organic reactions taking place in the organism in mild conditions and with a great specificity. Different esterases fulfill this role. Messengers, by transmitting messages to regulate biological processes; this function is done by i.e. insulin etc.. Transporters of other molecules through membranes Stocks of amino acids.
Regulatory roles are performed by globular proteins rather than fibrous proteins. Structural proteins, e.g. actin and tubulin, which are globular and soluble as monomers, but polymerize to form long, stiff fibers Among the most known globular proteins is hemoglobin, a member of the globin protein family. Other globular proteins are the alpha and gamma globulin. See protein electrophoresis for more information on the different globulins. Nearly all enzymes with major metabolic functions are globular in shape, as well as many signal transduction proteins. Albumins are globular proteins, unlike all of the other globular proteins, they are soluble in water, they are not soluble in oil
The lipid bilayer is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets; the cell membranes of all organisms and many viruses are made of a lipid bilayer, as are the nuclear membrane surrounding the cell nucleus, other membranes surrounding sub-cellular structures. The lipid bilayer is the barrier that keeps ions and other molecules where they are needed and prevents them from diffusing into areas where they should not be. Lipid bilayers are ideally suited to this role though they are only a few nanometers in width, they are impermeable to most water-soluble molecules. Bilayers are impermeable to ions, which allows cells to regulate salt concentrations and pH by transporting ions across their membranes using proteins called ion pumps. Biological bilayers are composed of amphiphilic phospholipids that have a hydrophilic phosphate head and a hydrophobic tail consisting of two fatty acid chains. Phospholipids with certain head groups can alter the surface chemistry of a bilayer and can, for example, serve as signals as well as "anchors" for other molecules in the membranes of cells.
Just like the heads, the tails of lipids can affect membrane properties, for instance by determining the phase of the bilayer. The bilayer can adopt a solid gel phase state at lower temperatures but undergo phase transition to a fluid state at higher temperatures, the chemical properties of the lipids' tails influence at which temperature this happens; the packing of lipids within the bilayer affects its mechanical properties, including its resistance to stretching and bending. Many of these properties have been studied with the use of artificial "model" bilayers produced in a lab. Vesicles made by model bilayers have been used clinically to deliver drugs. Biological membranes include several types of molecules other than phospholipids. A important example in animal cells is cholesterol, which helps strengthen the bilayer and decrease its permeability. Cholesterol helps regulate the activity of certain integral membrane proteins. Integral membrane proteins function when incorporated into a lipid bilayer, they are held to lipid bilayer with the help of an annular lipid shell.
Because bilayers define the boundaries of the cell and its compartments, these membrane proteins are involved in many intra- and inter-cellular signaling processes. Certain kinds of membrane proteins are involved in the process of fusing two bilayers together; this fusion allows the joining of two distinct structures as in the fertilization of an egg by sperm or the entry of a virus into a cell. Because lipid bilayers are quite fragile and invisible in a traditional microscope, they are a challenge to study. Experiments on bilayers require advanced techniques like electron microscopy and atomic force microscopy; when phospholipids are exposed to water, they self-assemble into a two-layered sheet with the hydrophobic tails pointing toward the center of the sheet. This arrangement results in two "leaflets"; the center of this bilayer contains no water and excludes molecules like sugars or salts that dissolve in water. The assembly process is driven by interactions between hydrophobic molecules. An increase in interactions between hydrophobic molecules allows water molecules to bond more with each other, increasing the entropy of the system.
This complex process includes non-covalent interactions such as van der Waals forces and hydrogen bonds. The lipid bilayer is thin compared to its lateral dimensions. If a typical mammalian cell were magnified to the size of a watermelon, the lipid bilayer making up the plasma membrane would be about as thick as a piece of office paper. Despite being only a few nanometers thick, the bilayer is composed of several distinct chemical regions across its cross-section; these regions and their interactions with the surrounding water have been characterized over the past several decades with x-ray reflectometry, neutron scattering and nuclear magnetic resonance techniques. The first region on either side of the bilayer is the hydrophilic headgroup; this portion of the membrane is hydrated and is around 0.8-0.9 nm thick. In phospholipid bilayers the phosphate group is located within this hydrated region 0.5 nm outside the hydrophobic core. In some cases, the hydrated region can extend much further, for instance in lipids with a large protein or long sugar chain grafted to the head.
One common example of such a modification in nature is the lipopolysaccharide coat on a bacterial outer membrane, which helps retain a water layer around the bacterium to prevent dehydration. Next to the hydrated region is an intermediate region, only hydrated; this boundary layer is 0.3 nm thick. Within this short distance, the water concentration drops from 2M on the headgroup side to nearly zero on the tail side; the hydrophobic core of the bilayer is 3-4 nm thick, but this value varies with chain length and chemistry. Core thickness varies with temperature, in particular near a phase transition. In many occurring bilayers, the compositions of the inner and outer membrane leaflets are different. In human red blood cells, the inner leaflet is composed of phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol and its phosphorylated derivatives. By contrast, the outer leaflet is based on phosphatidylcholine, sphingomyelin and a variety of gly
Fluid mosaic model
The fluid mosaic model explains various observations regarding the structure of functional cell membranes. According to this model, there is a lipid bilayer; the lipid bilayer gives elasticity to the membrane. Small amounts of carbohydrates are found in cell membrane; the model, devised by SJ Singer and GL Nicolson in 1972, describes the cell membrane as a two-dimensional liquid that restricts the lateral diffusion of membrane components. Such domains are defined by the existence of regions within the membrane with special lipid and protein composition that promote the formation of lipid rafts or protein and glycoprotein complexes. Another way to define membrane domains is the association of the lipid membrane with the cytoskeleton filaments and the extracellular matrix through membrane proteins; the current model describes important features relevant to many cellular processes, including: cell-cell signaling, cell division, membrane budding, cell fusion. The fluid mosaic model is the most acceptable model of plasma membrane.
Its main function is to give shape to the cell. Chemically a cell membrane is composed of four components: Phospholipids, Proteins and Cholesterol; the fluid property of functional biological membranes had been determined through labeling experiments, x-ray diffraction, calorimetry. These studies showed that integral membrane proteins diffuse at rates affected by the viscosity of the lipid bilayer in which they were embedded, demonstrated that the molecules within the cell membrane are dynamic rather than static. Previous models of biological membranes included the Robertson Unit Membrane Model and the Davidson-Danielli Tri-Layer model; these models had proteins present as sheets neighboring a lipid layer, rather than incorporated into the phospholipid bilayer. Other models described regular units of protein and lipid; these models were not well supported by microscopy and thermodynamic data, did not accommodate evidence for dynamic membrane properties. An important experiment that provided evidence supporting fluid and dynamic biological was performed by Frye and Edidin.
They used Sendai virus to force human and mouse cells to form a heterokaryon. Using antibody staining, they were able to show that the mouse and human proteins remained segregated to separate halves of the heterokaryon a short time after cell fusion. However, the proteins diffused and over time the border between the two halves was lost. Lowering the temperature slowed the rate of this diffusion by causing the membrane phospholipids to transition from a fluid to a gel phase. Singer and Nicholson rationalized the results of these experiments using their fluid mosaic model; the fluid mosaic model explains changes in structure and behavior of cell membranes under different temperatures, as well as the association of membrane proteins with the membranes. While Singer and Nicolson had substantial evidence drawn from multiple subfields to support their model, recent advances in fluorescence microscopy and structural biology have validated the fluid mosaic nature of cell membranes. Additionally, the two leaflets of biological membranes are asymmetric and divided into subdomains composed of specific proteins or lipids, allowing spatial segregation of biological processes associated with membranes.
Cholesterol and cholesterol-interacting proteins can concentrate into lipid rafts and constrain cell signaling processes to only these rafts. Another form of asymmetry was shown by the work of Mouritsen and Bloom in 1984, where they proposed a Mattress Model of lipid-protein interactions to address the biophysical evidence that the membrane can range in thickness and hydrophobicity of proteins; the existence of non-bilayer lipid formations with important biological functions was confirmed subsequent to publication of the fluid mosaic model. These membrane structures may be useful when the cell needs to propagate a non bilayer form, which occurs during cell division and the formation of a gap junction; the membrane bilayer is not always flat. Local curvature of the membrane can be caused by the asymmetry and non-bilayer organization of lipids as discussed above. More dramatic and functional curvature is achieved through BAR domains, which bind to phosphatidylinositol on the membrane surface, assisting in vesicle formation, organelle formation and cell division.
Curvature development is in constant flux and contributes to the dynamic nature of biological membranes. During the decade of 1970, it was acknowledged that individual lipid molecules undergo free lateral diffusion within each of the layers of the lipid membrane. Diffusion occurs at a high speed, with an average lipid molecule diffusing ~2 µm the length of a large bacterial cell, in about 1 second, it has been observed that individual lipid molecules rotate around their own axis. Moreover, phospholipid molecules can, although they do, migrate from one side of the lipid bilayer to the other. However, flip-flop might be enhanced by flippase enzymes; the processes described above influence the disordered nature of lipid molecules and interacting proteins in the lipid membranes, with consequences to membrane fluidity, signaling and function. There are restrictions to the lateral mobility of the lipid and protein components in the fluid membrane imposed by the formation of subdomains within the lipid bilayer.
These subdomains arise by several processes e.g. binding of membrane components to the extracellular matrix, nanometric membrane regions with a particular biochemical composition that promote the formation of lipid rafts and protein complexes mediated by protein-protein interactions. Furthermore, protein-cytos