Structure of Membrane Proteins

Helices that form pores will be amphiphilic because it is more favorable to have situated in the inner side of the pore hydrophilic amino acid side chains, while the outer side of the pore represents a more favorable environment for hydrophobic amino acid side chains since these are in contact with lipids. Some authors point to the possibility that such a structure contains hydrogen bonds between amino acid residues and the main chain in order to compensate opposite charges and oppositely oriented dipoles. A comparison between the strength of different interactions in the structure of soluble and membrane proteins leads to the conclusion that because of the decreased strength of hydrophobic interactions and increased strength of electrostatic interactions (because of the reduced dielectric constant), the electrostatic interactions play the main role in stabilizing the structure of membrane proteins.  

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Structure of Membrane Protein.s Membrane and Cell-Surface... 

Mutations that affect the structure of membrane proteins (teceptots, ttanspotters, ion channels, enzymes, and stmctutal proteins) may cause diseases examples include cystic fibrosis and familial hypetcholes-terolemia. 

If we had asked this question a few years ago, the answer would have been at best equivocal. However, as was pointed out in an earlier chapter, since the enormous progress in the determination of the structure of membrane proteins, we can, on the basis of the X-ray structures of an increasing number of ion transport proteins, begin to advance hypotheses that have more and more likelihood to be close to reality. In the case of Na+ channels we are still pretty much in the dark. However, the successful determination of the structure of a number of K+ channels of both bacterial and mammalian origins represents a great leap forward in our understanding of how these channels function. 

Good discussion of the secondary and tertiary structures of membrane proteins and the factors that stabilize them. 

Fariselli, P., Compiani, M. Casadio, R. (1993). Predicting secondary structure of membrane proteins with neural networks. Eur Biophys J 22,41-51. 

X-Ray diffraction analysis is a suitable and convenient method for obtaining exact structures of membrane proteins, but it requires three-dimensional crystals. Membrane protein crystallization has always... 

A method based on factor analysis followed by correlation of the factor loadings with structural composition has recently been proposed. This technique involves constructing a calibration set from infrared spectra of proteins whose secondary structure has been determined by X-ray. Factor analysis creates series of abstract spectra, which are combined to generate the original spectrum (Lee et al., 1990). This procedure was employed to estimate the secondary structures of membrane proteins (Lee et al., 1991). 

Cierpicki T, Liang B, Tamm LK, Bushweller JH. Increasing the accuracy of solution NMR structures of membrane proteins by application of residual dipolar couplings. High-resolution structure of outer membrane protein A. J. Am. Chem. Soc. 2006 128 6947-6951. 

Although membrane proteins are more difficult to purify and crystallize than are water-soluble proteins, researchers using x-ray crystallographic or electron microscopic methods have determined the three-dimensional structures of more than 20 such proteins at sufficiently high resolution to discern the molecular details. As noted in Chapter 3. the structures of membrane proteins differ from those of soluble proteins with regard to the distribution of hydrophobic and hydrophilic groups. We will consider the structures of three membrane proteins in some detail. 

Most of this chapter is devoted to the modeling of globular proteins because very few structures of membrane proteins have been experimentally determined. To date, the structures that have been determined belong to only two different classes, helical... 

There is much more awareness of the possible effect of the electric fields normal to the plane of the membrane on the structure and on the function of membrane proteins. However, no such relation was experimentally documented. There is an appreciable amount of information on the potential dependence of channel conductance, which is assumed to be caused by shifts of charged groups within the channel (41). These shifts correspond to small changes in conformation that could not be detected by methods sensitive to the secondary structure of the proteins. In the present and in some previous reports (7, 8), we have shown that membrane potentials of comparable magnitude to the physiological membrane potentials are sufficient to modulate the secondary structure of membrane proteins. The effect may be direct or indirect. The indirect effect shifts part of the molecular fraction immersed... 

FT-IR spectroscopy is particularly useful for probing the structure of membrane proteins. Until recently, a lack of adequate experimental techniques has been the reason for the poor understanchng of the secondary structure of most membrane proteins. X-ray diffraction requires high quality crystals and these are not available for many membrane proteins. Circular dichroism (CD) has been widely used for studying the conformation of water-soluble proteins, but problems arise in its use for membrane proteins. The light scattering effect may distort CD spectra and lead to substantial errors in their interpretation. In addition, the reference spectra used for the analysis of CD spectra are based on globular proteins in aqueous solution and may not be applicable to membrane proteins in the hydrophobic environment of lipid bilayers. 

The spatial structure of membrane proteins may also be elucidated by electron microscopy of the so-called 2D crystal. This method has been used to solve the 3D structure of bacteriorhodopsin with a resolution of 3.5 A. Some membrane proteins form ordered lattices in the membrane plane creating 2D crystals (ordered mono-... 

It is generally believed that the structure of membrane proteins is simpler than that of soluble proteins because the lipid bilayer in which the membrane proteins are immersed diminishes the degrees of freedom. Thus, the prediction of the membrane protein structures is expected to be more accurate and the obtained models should be of considerable help when the activity of the membrane proteins is analyzed. 

Insufficiently Reliable SWISS-PROT Structures of Membrane Proteins... 

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