Cell membrane extrinsic proteins

Thus, the fat globules are surrounded, at least initially, by a membrane typical of eukaryotic cells. Membranes are a conspicuous feature of all cells and may represent 80% of the dry weight of some cells. They serve as barriers separating aqueous compartments with different solute composition and as the structural base on which many enzymes and transport systems are located. Although there is considerable variation, the typical composition of membranes is about 40% lipid and 60% protein. The lipids are mostly polar (nearly all the polar lipids in cells are located in the membranes), principally phospholipids and cholesterol in varying proportions. Membranes contain several proteins, perhaps up to 100 in complex membranes. Some of the proteins, referred to as extrinsic or peripheral, are loosely attached to the membrane surface and are easily removed by mild extraction procedures. The intrinsic or integral proteins, about 70% of the total protein, are tightly bound to the lipid portion and are removed only by severe treatment, e.g. by SDS or urea. 

The cell membrane is associated with intrinsic and extrinsic proteins. Intrinsic proteins are globular proteins that generally span the bilayer and are held within the membrane by hydrophobic and electrostatic interactions. The proteins can form channels, carriers, or pumps that enable polar molecules to cross the membrane. 

Fig. 3 Structural model of the cell membrane. The membrane is composed of a bimolecular leaflet of phospholipid with the polar head groups facing the extracellular and cytosolic compartments and the acyl groups in the middle of the bilayer. Integral membrane proteins are embedded in the lipid bilayer. Integral proteins are glycosylated on the exterior surface and may be phosphorylated on the cytoplasmic surface. Extrinsic membrane proteins, peripheral proteins, are linked to the cytosolic surface of the intrinsic proteins by electrostatic interactions. (From Ref. l)...

The first complex to form is almost certainly the extrinsic factor X activation complex. Factor Vila binds to tissue factor, an integral membrane protein that is exposed upon injury of the blood vessel. The phospholipid bilayer surface is provided by the damaged cell membranes. In vivo, Ca + is always present in the blood. ... 

Studies on Thermotoga maritima have been focusing mainly on evolution, metabolism, and the correlation of protein structure and stability. It has been established that viability of the hyperthermophile in its hostile natural habitats is based on the inherent thermostability of its whole cell inventory. In some cases this is assisted by extrinsic components such as the cell membrane or specific ligands and compatible solutes. As a response to short-term temperature... 

These lipid bilayers are not very permeable towards a variety of molecules. Nevertheless, for cell metabolism and growth to occur, molecules such as sugars and amino acids must enter the ceil. Specific transport of this type is accomplished by proteins which are incorporated within the bilayer membrane. The protein serves as a carrier and the tjrpe of transport can be defined as carrier-mediated transport. The cell membrane consists of two main components the lipid bilayer which is the backbone, whereas the proteins take care of the specific transport functions. Some of the proteins are located on the outside of the lipid bilayer (the extrinsic proteins), whereas other proteins (the intrinsic proteins), completely penetrate through the lipid bilayer. The intrinsic proteins especially... 

The plasma membrane (Figure 9.3 ) is a phospholipid bilayer which incorporates various proteins and cholesterol. In eukaryotic cells, all membrane proteins expose at least one oligosaccharide chain to the outside of the cell, never to the inside. Some glycoproteins bind externally to the polar groups of the phospholipid and are termed peripheral (or extrinsic) proteins. Other proteins from the extracellular milieu may in turn adhere to these proteins. Proteins termed integral (or intrinsic) proteins appear positioned within the membrane from which, unlike the loosely bound peripheral proteins, they are not readily displaced. All integral proteins contain within their structure at least one hydrophobic segment which embeds within the membrane. Additionally, there may be a substantial hydrophilic polypeptide mass exposed... 

This fluid-mosaic membrane model allows proteins their freedom to diffuse in the plane of the lipid membrane and hence to become distributed over the cell surface in a pattern that is sometimes random and sometimes homogeneous (Singer and Nicolson, 1972). There are (a) integral proteins running perpendicularly to the plane of the lipid layer, some passing right through the bilayer, others only half way, and (b) extrinsic proteins that have become adsorbed on one or other of the surfaces of the bilayer and are easily lost. 

Extrinsic Pathway. Coagulation is initiated when tissue extracts with Hpid—protein properties are released from the membranes of endothehal cells following injury or insult. These substances, collectively designated tissue thromboplastin, complex with circulating Factor VII and in the presence of calcium ions subsequentiy activate Factor X (Fig. 1). In vitro evidence suggests that Factor X can be activated less rapidly through the interaction of kaUikrein [9001-01-8] with Factor VII. 

The interaction of an extrinsic membrane protein with a lipid bilayer can also be investigated by energy transfer. The interaction of cytochrome c has attracted much attention, and in an early study by Shaklai et al.(()5> the number of binding sites per red cell was determined. It was shown that an equation analogous to the Stem-Volmer relationship could be derived ... 

The extrinsic pathway consists of a series of events initially induced by death receptors located on the cell surface. It is initiated by interaction of extracellular death ligands with their respective receptors, located on the surface of the plasma membrane. The death ligands are members of the tumor necrosis factor (TNF)/nerve growth factor (NGF) superfamily. TNF-R1, Fas (Apo-l/CD95), TRAIL-R1, TRAIL-R2, and NGF-R are examples of death receptors. They are transmembrane proteins consisting of an external domain, where the ligand associates, and a cytoplasmic domain, which contains the DD (death domain). 

TNF is a cytokine produced mainly by activated macrophages, and is the major extrinsic mediator of apoptosis. Most cells in the human body have two receptors for TNF TNF-Rl and TNF-R2. The binding of TNF to TNF-Rl has been shown to initiate the pathway that leads to caspase activation via the intermediate membrane proteins TNF receptor-associated death domain (TRADD) and Fas-associated death domain (FADD). The link between TNF and apoptosis shows why an abnormal production of TNF plays a fundamental role in several human diseases, especially autoimmune diseases (see Chapter 15). 

The extrinsic pathway is mediated by tissue factor (TF), also known as thromboplastin or factor HI (Fig. 11.6a). Tissue factor is not present in blood plasma, i.e., it is extrinsic or outside of the vascular system. TF is a membrane protein that becomes exposed to the blood by trauma to the endothelial surface of blood vessels. It is especially rich in the membranes of pericytes, platelets, and leukocytes, but present in lesser amounts in most cells. It is absent from striated muscle cells and chondroblasts. 

Two pathways initiate a fibrin clot. Extrinsic path is mediated by tissue factor, also called thromboplastin. This membrane protein is exposed when pericytes are damaged. It binds to factor Vila in blood. Factor Vila is a protease and the phospholipid-VIIa-TF complex activates (converts) factor X by cleaving it to Xa. Intrinsic path is initiated by factor XII (Hageman factor), whose conformation is changed to a protease (XHa) by contact with a negatively charged surface such as RNA from damaged or necrotic cells. 

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