On Transmembrane Proteins

FIGURE 13.5 Principal component analysis. The transmembrane (black) and nontransmembrane (gray) segments form two different clusters. 

Training and Test Sets of Transmembrane and Non-Transmembrane Segments 

Finally, the 20-dimensional vectors based on the decagonal isometric matrix were used to represent the transmembrane and non-transmembrane segments. When used to train and optimize a CPNN network, the following configuration for the optimized network was found the network size, 40 x 40 the number of epochs, 500 and the maximum correction factor, 0.5. The network shows 14.3% error in recall ability and 27.1% error in prediction ability with error threshold at 0.501. 

With the growing number of proteins sequenced, there is a necessity for novel techniques to analyze protein sequences in order to determine their structure and function. The most commonly used protein sequence descriptors are based on evolutionary information and physicochemical properties. Even though these methods have proven to be efficient in most cases, in cases of transmembrane proteins, they may fall short. As the vast field of transmembrane proteins largely remains unexplored with many transmembrane proteins yet to be sequenced, it is possible to obtain new protein sequences without any known homolog. In such cases, traditional sequence analysis methods based on alignment profiles would not be sufficient. The evolutionary information-based descriptors appear inadequate, and indices based on physicochemical property can cause ambiguities. Therefore, it is of considerable interest to develop novel methods based on sequence information alone to represent protein sequences. 

The two matrix representations of the protein segments, the amino acid adjacency matrix and the decagonal isometries matrix, are derived from the sequence information alone. As has been demonstrated, mathematical descriptors, dependent on the sequence information alone, have successfully revealed the underlying characteristics and patterns of given sequences. Their numerical nature also makes them easier to incorporate into a mathematical model. In addition, as has been well illustrated in chemical graph theory, when considering characterization of molecules, one can 

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Altenbach, C., et al. (1989). Structural studies on transmembrane proteins. 2. Spin labeling of bacteriorhodopsin mutants at unique cysteines. Biochemistry 28, 7806—7812. 

One of the striking applications of electroporation is incorporation of externally added protein into plasma membrane. Protein molecules with amphipathic nature can be stably entrapped in electroporated membrane when they reseal. This phenomenon called electroinsertion has been demonstrated in a number of investigations. For example, electroinsertion of transmembrane protein CD4 receptors [60] and glycophorin [61] was demonstrated, which may prove valuable in surface engineering and studies on transmembrane proteins. In addition, a number of exogenous peptides and protein enzymes have been introduced... 

Plexins comprise a family of transmembrane proteins that serve as receptors for semaphorins. On the basis... 

Syndecans are transmembrane proteins, which are modified by the addition of heparan sulphate glycos-aminoglycan (GAG) chains and other sugars. Syndecans bind a wide variety of different ligands via their heparan sulphate chains. Binding specificities may vary depending on cell-type specific modifications of the heparan sulphate chains. 

TLRs are transmembrane proteins found on the plasma membrane and on endosomal membranes. The ability of the TLRs to recognise microbial products comes from the 19-25 copies of the LRR motif. The differences in these LRRs are what give the TLRs the ability to bind different components of pathogens. 

Vitamin K carboxylase is a transmembraneous protein in the lipid bilayer of the endoplasmatic reticulum (ER). It is highly glycosilated and its C-terminal is on the luminal side of the membrane. Besides its function as carboxylase it takes part as an epoxidase in the vitamin K cycle (Fig. 1). For the binding of the y-carboxylase the vitamin K-dependent proteins have highly conserved special recognition sites. Most vitamin K-dependent proteins are carboxy-lated in the liver and in osteoblasts, but also other tissues might be involved, e.g., muscles. 

Figure 46-5. Variations in the way in which proteins are inserted into membranes. This schematic representation, which illustrates a number of possible orientations, shows the segments of the proteins within the membrane as a-helicesand the other segments as lines. The LDL receptor, which crosses the membrane once and has its amino terminal on the exterior, is called a type I transmembrane protein. The asialoglycoprotein receptor, which also crosses the membrane once but has its carboxyl terminal on the exterior, is called a type II transmembrane protein. The various transporters indicated (eg, glucose) cross the membrane a number of times and are called type III transmembrane proteins they are also referred to as polytopic membrane proteins. (N, amino terminal C, carboxyl terminal.) (Adapted, with permission, from Wickner WT, Lodish HF Multiple mechanisms of protein insertion into and across membranes. Science 1985 230 400. Copyright 1985 by the American Association for the Advancement of Science.)...

Studies of other members of the family have also added support to the topological model shown in the Fig. 3. In particular, chemical labelling of the native and mutated tetracycline transporter has confirmed the cytoplasmic location of the N-terminus and the loop connecting transmembrane helices 2 and 3 [231,232]. Protease digestion experiments on this protein have also provided preliminary evidence for the cyto-... 

The artificial lipid bilayer is often prepared via the vesicle-fusion method [8]. In the vesicle fusion process, immersing a solid substrate in a vesicle dispersion solution induces adsorption and rupture of the vesicles on the substrate, which yields a planar and continuous lipid bilayer structure (Figure 13.1) [9]. The Langmuir-Blodgett transfer process is also a useful method [10]. These artificial lipid bilayers can support various biomolecules [11-16]. However, we have to take care because some transmembrane proteins incorporated in these artificial lipid bilayers interact directly with the substrate surface due to a lack of sufficient space between the bilayer and the substrate. This alters the native properties of the proteins and prohibits free diffusion in the lipid bilayer [17[. To avoid this undesirable situation, polymer-supported bilayers [7, 18, 19] or tethered bilayers [20, 21] are used. 

A type I transmembrane protein called endothelial cell protein C receptor (EPCR), which is expressed at high levels exclusively on a subset of endothelial cells, has also been identified. EPCR has a role in the protein C pathway (30). EPCR binds to both protein C and activated protein C (APC) with equal affinity. Activation of protein C presumably requires interaction of the protein C-EPCR complex with the thrombin-thrombomodulin complex. APC that is formed as a result of this interaction is reversibly bound to EPCR until it dissociates to react subsequently with protein S. The APC-protein S complex inactivates activated factor V (Va). 

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