Transmembrane prediction

Alpha helices that cross membranes are in a hydrophobic environment. Therefore, most of their side chains are hydrophobic. Long regions of hydrophobic residues in the amino acid sequence of a protein that is membrane-bound can therefore be predicted with a high degree of confidence to be transmembrane helices, as will be discussed in Chapter 12. 

Since the outside of the barrel faces hydrophobic lipids of the membrane and the inside forms the solvent-exposed channel, one would expect the P strands to contain alternating hydrophobic and hydrophilic side chains. This requirement is not strict, however, because internal residues can be hydrophobic if they are in contact with hydrophobic residues from loop regions. The prediction of transmembrane p strands from amino acid sequences is therefore more difficult and less reliable than the prediction of transmembrane a helices. 

Transmembrane a helices can be predicted from amino acid sequences... 

In contrast, the transmembrane helices observed in the reaction center are embedded in a hydrophobic surrounding and are built up from continuous regions of predominantly hydrophobic amino acids. To span the lipid bilayer, a minimum of about 20 amino acids are required. In the photosynthetic reaction center these a helices each comprise about 25 to 30 residues, some of which extend outside the hydrophobic part of the membrane. From the amino acid sequences of the polypeptide chains, the regions that comprise the transmembrane helices can be predicted with reasonable confidence. 

The hydropathy plots in Figure 12.23 were calculated and published several years before the x-ray structure of the reaction center was known. It is therefore of considerable interest to compare the predicted positions of the transmembrane-spanning helices with those actually observed in the x-ray structure. These observed positions are indicated in green in Figure 12.23. 

The most important general lesson is that there are hydrophobic transmembrane helices, the positions of which within the amino acid sequence can be predicted with reasonable accuracy. This applies both to the single transmembrane-spanning helix within the H polypeptide chain of the reaction center and the five transmembrane helices of the L and M chains that... 

Fasman, G.D., Gilbert, W.A. The prediction of transmembrane protein sequences and their conformation an evaluation. Trends Biochem. Sci. 15 89-95, 1990. 

Fasman, G. D., and Gilbert, W. A., 1990. The prediction of transmembrane protein sequences and dieir conformation An evaluation. Trends in Biochemical Sciences 15 89—92. 

Starting from the protein sequence (primary structure) several algorithms can be used to analyze the primary structure and to predict secondary structural elements like beta-strands, turns, and helices. The first algorithms from Chou and Fasman occurred already in 1978. The latest algorithms find e.g., that predictions of transmembrane... 

Figure 3.4 Transmembrane topology of a 7-TM domain G-protein receptor such as the P-adrenoceptor. Agonist binding is predicted to be within the transmembrane domains. The extracellular structure is stabilised by the disulphide bond joining the first and second extracellular loop. The third intracellular loop is the main site of G-protein interaction while the third intracellular loop and carboxy tail are targets for phosphorylation by kinases responsible for initiating receptor desensitisation...

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