Mosaic protein

Mochizuki N, Cho G, Wen B, Insel PA (1996) Identification and cDNA cloning of a novel human mosaic protein, LGN, based on interaction with G alpha i2. Gene 181 39 3 Mochizuki N, Ohba Y, Kiyokawa E, Kurata T, Murakami T, Ozaki T, Kitabatake A, Nagashima K, Matsuda M (1999) Activation of the ERK/MAPK pathway by an isoform of raplGAP associated with G alphaff). Nature 400 891-894... 

The main function of these two subclasses is to produce the semipermeable lipid bilayer membrane structure of the cell. The current model of a cell membrane is referred to as fluid mosaic. Proteins and cholesterol are also incorporated with the bilayer for purposes of stability, permeability, and cell recognition. 

Describe the proposed domain structure of the LDL receptor derived from the primary sequence of this protein. Define the term mosaic protein. 

The cytoplasmic domains of all of these receptors have an intrinsic protein tyrosine kinase activity, and all the receptors have hydrophobic transmembrane sequences. Their extracellular regions are more variable in stmcture. Depending on the receptor, they may contain a range of domains, including (1) immrmoglobulin domains, (2) cysteine-rich motifs, (3) fibronectin type III repeats, and (4) EGF motifs. These can be present singly or in different combinations. Growth factor receptors are therefore examples of mosaic proteins. 

Biological membranes provide the essential barrier between cells and the organelles of which cells are composed. Cellular membranes are complicated extensive biomolecular sheetlike structures, mostly fonned by lipid molecules held together by cooperative nonco-valent interactions. A membrane is not a static structure, but rather a complex dynamical two-dimensional liquid crystalline fluid mosaic of oriented proteins and lipids. A number of experimental approaches can be used to investigate and characterize biological membranes. However, the complexity of membranes is such that experimental data remain very difficult to interpret at the microscopic level. In recent years, computational studies of membranes based on detailed atomic models, as summarized in Chapter 21, have greatly increased the ability to interpret experimental data, yielding a much-improved picture of the structure and dynamics of lipid bilayers and the relationship of those properties to membrane function [21]. 

Bloomer, A.C., et al. Protein disk of tobacco mosaic virus at 2.8 A resolution showing the interactions within and between subunits. Nature TIB-. 362-368, 1978. 

A nucleic acid can never code for a single protein molecule that is big enough to enclose and protect it. Therefore, the protein shell of viruses is built up from many copies of one or a few polypeptide chains. The simplest viruses have just one type of capsid polypeptide chain, which forms either a rod-shaped or a roughly spherical shell around the nucleic acid. The simplest such viruses whose three-dimensional structures are known are plant and insect viruses the rod-shaped tobacco mosaic virus, the spherical satellite tobacco necrosis virus, tomato bushy stunt virus, southern bean mosaic vims. 

Antiparallel tt-helix proteins are structures heavily dominated by a-helices. The simplest way to pack helices is in an antiparallel manner, and most of the proteins in this class consist of bundles of antiparallel helices. Many of these exhibit a slight (15°) left-handed twist of the helix bundle. Figure 6.29 shows a representative sample of antiparallel a-helix proteins. Many of these are regular, uniform structures, but in a few cases (uteroglobin, for example) one of the helices is tilted away from the bundle. Tobacco mosaic virus protein has small, highly... 

FIGURE 6.38 A sampling of proteins that consist of mosaics of individual protein modules. The modules shown include 7CG, a module containing 7-carboxyglutamate residues G, an epidermal growth-factor-like module K, the kringle domain, named for a Danish pastry ... 

In 1972, S. J. Singer and G. L. Nicolson proposed the fluid mosaic model for membrane structure, which suggested that membranes are dynamic structures composed of proteins and phospholipids. In this model, the phospholipid bilayer is a fluid matrix, in essence, a two-dimensional solvent for proteins. Both lipids and proteins are capable of rotational and lateral movement. 

FIGURE 9.6 The fluid mosaic model of membrane structure proposed by S. J. Singer and G. L. Nicolsou. In this model, the lipids and proteins are assumed to be mobile, so that they can move rapidly and laterally in the plane of the membrane. Transverse motion may also occur, but it is much slower. 

Membrane proteins in many cases are randomly distributed through the plane of the membrane. This was one of the corollaries of the fluid mosaic model of Singer and Nicholson and has been experimentally verified using electron microscopy. Electron micrographs show that integral membrane proteins are often randomly distributed in the membrane, with no apparent long-range order. 

Hurst (19) discusses the similarity in action of the pyrethrins and of DDT as indicated by a dispersant action on the lipids of insect cuticle and internal tissue. He has developed an elaborate theory of contact insecticidal action but provides no experimental data. Hurst believes that the susceptibility to insecticides depends partially on the cuticular permeability, but more fundamentally on the effects on internal tissue receptors which control oxidative metabolism or oxidative enzyme systems. The access of pyrethrins to insects, for example, is facilitated by adsorption and storage in the lipophilic layers of the epicuticle. The epicuticle is to be regarded as a lipoprotein mosaic consisting of alternating patches of lipid and protein receptors which are sites of oxidase activity. Such a condition exists in both the hydrophilic type of cuticle found in larvae of Calliphora and Phormia and in the waxy cuticle of Tenebrio larvae. Hurst explains pyrethrinization as a preliminary narcosis or knockdown phase in which oxidase action is blocked by adsorption of the insecticide on the lipoprotein tissue components, followed by death when further dispersant action of the insecticide results in an irreversible increase in the phenoloxidase activity as a result of the displacement of protective lipids. This increase in phenoloxidase activity is accompanied by the accumulation of toxic quinoid metabolites in the blood and tissues—for example, O-quinones which would block substrate access to normal enzyme systems. The varying degrees of susceptibility shown by different insect species to an insecticide may be explainable not only in terms of differences in cuticle make-up but also as internal factors associated with the stability of oxidase systems. 

Fraser, R.S.S. (1982). Are pathogenesis-related proteins involved in acquired systemic resistance of tobacco plants to tobacco mosaic virus Journal of General Virology, 58, 305-13. 

P] Halstrom, J., Kovdcs, K., Bninfeldt, K. Synthesis of the N-lVityl Hex ieplide Hydrazide Corresponding to the Sequence 152-157 of the Coat Protein of Tbbacco Mosaic Virus. Comparison of the Homogeneous and the Solid Phase Syntheses", Acta Chem. Scand. 1973, 27. 3085-3090. 

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