Explain, giving cases, the way the structural features of membrane proteins are related to their functions.
Membrane proteins are protein substances that have any kind of connection with the membrane of a cell or organelle, and are normally split into two different communities: essential and peripheral membrane proteins. As stated by Earnshaw & Pollard (2002), essential proteins go through the membrane, whilst peripheral protein only relate with either the within or outside surfaces of the lipid bilayer. Membrane protein have a variety of functions, and their structures are well adapted for this. There are placed the membrane proteins into three categories (although they do overlap sometimes) - receptors and cell signalling; cell adhesion molecules, and transport proteins - and can proceed through each category describing the relationship between framework and function.
Cell communication is the main function of receptors, allowing cells to discover what is going on around them, and permitting them to then respond and respond consequently. The transmission transduction pathway is the procedure that takes place when a transmission on the cell's surface is altered in several periods, into a certain mobile response, which is in this pathway that receptors play their part. We are told by Earnshaw & Pollard (2002) they can be stimulated by lots of types of signalling molecules, for example, nutrition, neurotransmitters, human hormones and progress factors, and through the transmission transduction pathway, can create a number of mobile responses like the electrical probable of the plasma membrane, gene appearance and enzyme activity. The majority of receptors on the target cell's surface are transmembrane protein (integral protein that span the entire membrane). Generally, receptors are extremely specific, and are formed and structured in such a way that they will only bind to a certain ligand, and this makes certain that the receptor can only be triggered by that type of ligand, producing a particular response.
Receptor tyrosine kinases (RTKs) are receptors which may have an extremely high affinity for a large number of progress factors and hormones, such as epidermal progress factor (stimulates proliferation of some cell types), platelet-derived expansion factor (stimulates, among others, success of some cell types), and insulin (stimulates health proteins synthesis), affirmed by Albert et al. (2002). There are around 16 structural subfamilies, and most of them (however, not all, for example the insulin receptor doesn't) consist of an individual polypeptide string that spans the entire membrane. The section that does indeed span the membrane tends to be composed of between 25 and 38 amino acids. The N-terminal region of the polypeptide string, which can be quite large in proportions (it can have anywhere between 15-100 residues attached), is extracellular, which is exactly what binds to the ligands. The C-terminal region of the polypeptide chain is intracellular which gets the domains present that are accountable for the kinase activity of these receptors.
For there to be activation of the kinase domains on the C-terminal of the receptor, there should be a conformational change in the receptor. As the receptor is only one chain, it must form a dimer or an increased oligomer (this is where two or more receptor molecules get together; the procedure known as oligomerisation). Earnshaw & Pollard (2002) suggest that at the C-terminals there are several tyrosine residues, so when the dimmers are shaped, they are able to cross-phosphorylate the other person - a process known as autophosphorylation. This escalates the kinase activity of the domain name and allows for easier binding between the docking sites and intracellular signalling protein inside the target cell, mentioned by Albert et al. (2002). For the RTK to be turned on, the ligand, whether it be a growth factor or hormone, normally must bind to two adjacent receptor chains simultaneously. The insulin receptor is an exemplory case of a RTK. It was believed by Weissmann et al. (1975) that the insulin receptor only been around externally surface of the membrane. However, more recent research instructs us that is inappropriate. Albert et al. (2002) instructs us that the receptor is a tetramer. Which means that it offers four polypeptide chains, two alpha and two beta. One alpha and one beta chain constitute a subunit, and are connected by disulfide bonds. Both subunits are therefore equivalent and constitute a well balanced dimer. The beta chains course the membrane and is connected to a cytoplasmic tyrosine kinase domain name. The alpha chains form the insulin-binding extracellular domain. When insulin binds to these alpha chains, a conformational change is brought about on the kinase domains - they are simply brought together and autophosphorylation occurs. This stimulates kinase activity, and finally contributes to the increase of sugar uptake from the bloodstream into muscle skin cells and adipose tissue.
G proteins (also called GTP-binding proteins and GTP-ases) are also receptor protein that are within the membrane and get excited about second messenger cascades. According to Albert et al. (2002) there are two specific sets of G-protein: heterotrimeric G protein and small GTP-ases, however, here I am going to concentrate on heterotrimeric G proteins.
Heterotrimeric G protein have 7 membrane domains and three subunits present on the internal surface of the cell membrane: Ga (this retains the binding site for GDP and GTP), G, and G?. Kimball (2007) shows that when the G health proteins is in an inactive condition, GDP is bound to Ga. When a ligand, for example a hormone, attaches itself to the G protein receptor externally of the cell membrane, there is a conformational change in the receptor. This causes a change in form in Ga, which in turn causes GTP to displace GDP. G and G? are dissociated from Ga, and form a dimer, whilst the triggered Ga switch on the effector molecule. Deactivation of the G health proteins require hydrolysis of GTP, producing GDP and inorganic phosphate, and the go back of the GG? dimer.
Cell adhesion substances (CAMs) are glycoproteins, and can either be cell-to-cell or cell-matrix adhesion substances, regarding to Albert et al. (2002). There are some CAMs that are calcium reliant, and others that are calcium 3rd party. Cadherins are calcium based mostly and are present in vertebrate tissues. The hydrophobic alpha helix pass through the membrane only once and are ranging from 700-750 proteins in length. It really is thought that the extracellular region of the polypeptide is folded into around 5 cadherin repeats and between each do it again are calcium mineral ions which lock the repeats together, building stiff rod-like set ups. These are in a position to interact and connect themselves to other substances of the same kind (known as the homophilic device) on adjacent cells by acting like an interlocking molecular zipper. Cadherins not only ensure that cells within tissue are firmly held together, they also indirectly link the actin cytoskeletons of the cells they join along. The cadherins have a cytoplasmic tail that, by making use of intracellular anchor proteins catenins, bind to the actin, and everything is strongly kept in place. There are various types of cadherins, for example N-cadherin (within neurons) and P-cadherins (within the placenta). The best known cadherin is E-cadherins, within adheren junctions in epithelial tissue and they're the first cadherins expressed during mammalian development. If the E-cadherin is not present or expressed, the effectiveness of mobile adhesion in a cells is decreased, signifying cells have the ability to move around. This is not at all good if tumors has produced, as its capacity to mix the basement membrane and invade near tissue is increased.
Integrins are marginally dissimilar to cadherins. These are calcium 3rd party and are heterophilic CAMs - able to bind to a variety of ligands, corresponding to Weissmann et al. (1975). They can be heterodimers, and have two polypeptide chains that course the membrane once: one alpha and one beta. The N-terminals of each polypeptide string protrude 16nm above the outside of the membrane, and this is what affiliates with the ligand. These parts of the polypeptides are constructed of different domains. The alpha chain has three domains folded similarly to immunoglobulins, the beta string has four epidermal growth factor (EGF) like domains. Bound to these chains are divalent cations, and it is believed that they connect to the acidic regions on the ligand and ensure its binding. The cytoplasmic tails of the integrins have the ability to interact with a number of different signalling proteins (connected by paxillin proteins), and this helps with its function of indication transduction. These 'tails' are associated with actin filaments via talin and vinculin protein (different proteins to what are used with cadherins).
It is thought by Weissmann et al. (1975) that lots of calcium 3rd party CAMs contain a number of immunoglobulin (Ig) like domains that are quality of antibody molecules. Neural cell adhesion molecule (NCAM), present in most neurons and skeletal muscle, is an excellent example of a calcium independent CAM. It binds to other skin cells in a homophilic device, which is believed that there are at least 27 forms of NCAM. The polypeptide has a sizable extracellular region which folds into five Ig-like domains, organised mutually by disulfide bonds. Sialic acid exists on the some forms of NCAM, and, because of its negative fee, it halts cell adhesion, and this is important in cell migration and invasion.
They are proteins that carry substances either in a cell (intracellular), through smooth outside the cell (extracellular) or through membranes. I will be focusing on the transport proteins that are from the membrane and there are a variety of different kinds of proteins that transport substances: carriers, channels and pumps. Earnshaw & Pollard (2002) state that carrier proteins are one polypeptide string that span the membrane around 12 times, which is supported by tests that show between 60-70% of the polypeptide chain is alpha helical - enough to create 12 helical membrane-spanning regions. However there are exceptions to this, for example service providers within mitochondria and chloroplasts are only half as long in length, and form homodimers to make up the length. Both N- and C-terminal are cytoplasmic. Carrier proteins provide reversible, passive pathways for specific solutes to mix the lipid bilayer down their attention gradient. The proteins has two conformational expresses. The first is when the binding sites of the protein is exposed on the outside of the membrane. Whenever a specific material binds with it, it takes in the product and retains it, whilst the shape of the protein itself changes (into its second conformational status) and the substance is currently facing the inside of the cell. Carrier proteins, use the ion/substrate gradient as a source of energy to execute other careers, for example travelling other substances up their awareness gradient. Glucose transporters (GLUT) are an example of membrane carriers, and corresponding to Professor Whitley (2008), there are five associates of the blood sugar transporter family: GLUT1 to GLUT5. Although they are all present in several tissues (GLUT2 within liver and pancreatic skin cells; GLUT4 within muscle and unwanted fat cells) each of them passively transport sugar in and out if skin cells (they are bidirectional transfer). They have got 12 membrane spanning domains, with both the N- and C-terminals on the cytoplasmic area. They are driven by amount gradients, and these gradients are retained by phosphorylation.
Channels are found in the majority of epithelial skin cells, though not in those of skeletal muscle and the nervous system. They can be ion specific and transport ions at a much faster rate than carrier protein. These channels have the ability to start and close in a regulated way, stated by Earnshaw & Pollard (2002), and once open, anticipated to electrical and focus gradients, ions have the ability to pass quickly over the membrane. Any changes in the activity of the route will lead to speedy electrical impulses to excitable membranes of nerves and muscles, as the electro-mechanical potential is manipulated by the activity of ions through the channels. Nearly all channels contain multiple subunits. A good example of a route is a K+ route, KcsA, and they have four equivalent subunits, each formulated with two transmembrane helices. Over the cytoplasmic aspect of the membrane the transmembrane helices are incredibly close collectively, however on the extracellular side, to allow for the selectivity filtration and pore helices, they may be more spread out. The pore moves all the way through the membrane, with a thin part that is specific in every K+ channels. It is formed by three residues in a certain sequence (GYG), which pore is just wide enough to allow a K+ ion to feed. Pumps, also known as primary productive transporters, use energy to transport solutes up their amount gradient. You can find various kinds of pumps carrying out virtually identical functions. Bacteriorhodopsin is a necessary protein used by Archaea that uses light energy to move protons out of the cell. The proton gradient developed is then used as energy. Explained by Earnshaw & Pollard (2002) there are two-dimensional crystalline areas within the plasma membrane formulated with the bacteriorhodopsin. It has seven alpha helices that cross the membrane and these have one molecule of retinal buried in them. When a photon is consumed the retinal molecule changes form, which leads to the conformational change of complete protein, and then the proton pumping action.
So far the transport proteins I have looked at have been transporting substances over the membrane. However transport through the extracellular substance is just as important, and it is believed glyophorin will this. Glycophorin is present on the outside surface of your red blood cell, and is also a glycoprotein. Corresponding to Albert et al. (2002) it has around 131 amino acids, with a lot of the mass on exterior area of the lipid bilayer, and goes by through the membrane only one time. It also has a big quantity of oligosaccharide chains attached to the extracellular parts. The N-terminal is extracellular, whilst the C-terminal is intracellular. It had been believed, as explained by Weissmann et al. (1975) that the function of glycophorin was either to carry sugar molecules in the blood vessels, or to help keep stability and shape within the red blood cell, as it tends to can be found as a homodimer and the hydrophobic parts are strong anchors. However, Albert et al. (2002) state that although there being nearly one million glycophorin proteins in each red bloodstream cell, their function is not yet known. Difference in view may be because of the fact that tests done in recent times have had the opportunity to cancel out what was actually assumed in 1975.
Through research I've found that membrane proteins may all be built from the same blocks (proteins) and have the same basic framework - primary, extra, tertiary and quaternary set ups - but can form into complex set ups that are really specific with their function. You will discover so many different functions that are carried out by membrane proteins, and these are only successful due to the specificity of the protein - this way the health proteins is folded, coiled, the way they connect to other molecules and the bonds that can be found within them.
- Albert, B. et al. (2002) Molecular Biology of the Cell. 4th edn. NY : Garland Technology.
- Earnshaw, W. & Pollard, T (2002) Cell Biology. U. S. A : Elsevier Science
- Kimball, J. (2007) G Proteins. [Online]. Offered by: http://users. rcn. com/jkimball. ma. ultranet/BiologyPages/G/G_Proteins. html (Accessed: 1st April 2008)
- Weissmann, G. et al. (1975) Cell Membranes, Biochemistry, Cell Biology & Pathology. New York : HP Posting Co.
- Professor Whitley, G (Semester 2, Week 2, 2008) 'Membrane Structure and Function I'