Spanning proteins

Cell membrane spanning proteins contain a luminal/ extracellular domain, a transmembrane region and a cytosolic domain. In a type I transmembrane protein the N-terminus is the extracellular/luminal part of the protein, whereas the C-terminus comprises the cytosolic region of the membrane protein. 

Calcium channels are members of the large family of proteins, including Na and channels, which become incorporated into plasma membranes, and which form intermittent aqueous pathways through which ions can move. The channels open and close. As is the case generally for membrane spanning proteins, a Ca channel is formed by a set of helical units, in this case seven, which associate to form the channel. 

The movement of solutes from the external environment into the cell is usually achieved using cell membrane-spanning proteins that facilitate solute transfer. These are necessary, since most solutes (e.g. sugars, amino acids, salts) will not readily diffuse through the hydrophobic cell membrane. Movement of solutes into the epithelial cell can involve a variety of protein carriers or channels including (see Figure 1) ... 

Symporters are membrane-spanning proteins which translocate two or more solutes in the same direction across the cell membrane. In epithelial tissue, such... 

Na+K+-ATPase a ubiquitous membrane-spanning protein, which uses ATP as a source of energy for moving ions, responsible for Na+ flux against the electrochemical gradient. 

Note that this classification does not cover all the theoretical possibilities. For example, a cleavable signal peptide cannot direct the creation of a topology opposite to a type I (according to the loop model). Why other types are not observed must be explained from their insertion mechanisms. This classification can be naturally expanded into multi-spanning proteins (polytopic proteins) based on the location of their N terminus (therefore, type IV cannot be defined). 

Owing to the small number of known peroxisomal membrane proteins, the signals (mPTSs) that direct them to the membrane are not well characterized. In one example, mPTS is found in the fourth loop (20 residues) of a 6 membrane-spanning protein. The loop faces to the matrix side. In another example, mPTS was found in the N-terminal 40-residue segment on the matrix side. Both of them contain a 5-residue stretch rich in basic amino acids and seem to be a part of the mPTS. 

Hartmann, E., Rapoport, T., and Lodish H. (1989). Predicting the orientation of eukaryotic membrane-spanning proteins. Proc. Natl. Acad. Sci. U.S.A. 86, 5786-5790. 

Klein, P., Kanehisa, M., and DeLisi, G. (1985). The detection and classification of membrane-spanning proteins. Biochim. Biophys. Acta 815, 468—476. 

The superfamily of seven-transmembrane C-protein-coupled receptors is the largest and most diverse group of membrane-spanning proteins [172]. Within all identified human genes, approximately 1,000 encode C-protein-coupled receptors. Many... 

Many proteins will not yield crystals in initial crystal trials. Unfortunately, crystallization is still a trial-and-error procedure, with no real way of predicting success or failure. If you fail to get crystals in your initial trials, it need not be the end of your structural studies (although it could be ). Many of the targets for neuroscientists are going to be membrane-bound or membrane-spanning proteins, and these are notoriously difficult to crystallize. Techniques are continuously being developed and refined to improve our ability to crystallize difficult protein examples. 

Table I gives a compilation of the molecular composition of SFV grown in BHK-21 cells, based on the revised weight for the viral particle of 41-42 X 10 daltons (Jacrot et al, 1983). If one assumes that each phospholipid-cholesterol pair takes up a surface area of about 90-100 A (Israelachvili and Mitchell, 1975) and each glycolipid about 55 A (Pascher and Sundell, 1977), then about 80% of the surface area in the bilayer is occupied by the lipids, leaving about 20% for the spanning proteins. This is somewhat more than would be expected if 180 spike proteins span the bilayer, each having two transmembrane a helical segments.

Overbaugh, J., Miller, A. and Eiden, M. (2001) Receptors and entry cofactors for retroviruses include single and multiple transmembrane-spanning proteins as well as newly described glycophosphatidylinositol-anchored and secreted proteins. Microbio. Mol. Biol. Reviews55, 371-389. 

All these pathways converge to modulate the activity of the enzyme, H+/K+ ATPase, the proton pump of the parietai ceii. This is a membrane-spanning protein, an ATP-dependent ion pump, exchanging K+ and H+ ions. 

While one end of the dystrophin molecule binds to actin filaments, the C-terminal domain associates with several additional proteins to form a dystrophin-glycoprotein complex (see figure)/1 k Dystrophin is linked directly to the membrane-spanning protein P-dystroglycan, which in the outer membrane surfaces associates with a glycoprotein a-dystroglycan. The latter binds to laminin-2 (Fig. 8-33), a protein that binds the cell to the basal lamina. Four... 

Integral transmembrane proteins often contain helical segments of the appropriate length to span the membrane. These helices are composed of hydrophobic amino acid residues. In transmembranous proteins with multiple segments that span the membrane, you may find some hydrophilic residue side chains. Why are hydrophilic side chains not favored in single-span membrane proteins How may the hydrophilic side chains be accommodated in multiple-span proteins ... 

All of the growth factors characterized so far are proteins (table 24.7). Many of them are cleaved from larger precursors. The 53-amino-acid epidermal growth factor (EGF) is cleaved from a precursor of 1,168 amino acids. This precursor is a membrane-spanning protein, with the EGF moiety and nine related sequences in the extracellular domain. EGF is homologous to several other growth factors,... 

MHC class II molecules are made up of two membrane-spanning proteins each chain has a size of 30 kDa and is made up of two globular domains. These domains are called a-1, a-2, (3-1 and P-2. Each chain possesses an immunoglobulin-like region next to the cell membrane. MHC class II molecules are highly polymorphic. 

The first identified cannabinoid receptor subtype, CB was cloned and demonstrated to have an amino acid sequence consistent with a tertiary structure typical of the seven transmembrane-spanning proteins that are coupled to G proteins. In addition to being found in the central nervous system, mRNA for CB has also been identified in testes. The central nervous system responses to cannabinoid compounds are believed to be mediated exclusively by CB, inasmuch as CB2 transcripts could not be found in brain tissue by either Northern analysis or in situ hybridization studies. CBj transduces signals in response to central-nervous-system-active constituents of C. sativa as well as synthetic bicyclic and tricyclic cannabinoid analogs, aminoalkylindole, and eicosanoid cannabimimetic compounds. CB is coupled to G, to inhibit adenylate cyclase activity and to a pertussis-sensitive G protein to regulate Ca2+ currents. 

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