Conformation of membrane proteins

Effects of anesthetics and lipid removal on some kinetic properties of mitochondrial ATPase and on conformation of membrane proteins (16, 19-21)... 

It is emphasized that revealing the dynamics as well as the structure (or conformation) based on several types of spin-relaxation times is undoubtedly a unique and indispensable means, only available from NMR techniques at ambient temperature of physiological significance. Usually, the structure data themselves are available also from X-ray diffraction studies in a more refined manner. Indeed, better structural data can be obtained at lower temperature by preventing the unnecessary molecular fluctuations, which are major subjects in this chapter, since structural data can be seriously deteriorated for domains where dynamics are predominant even in the 2D or 3D crystalline state or proteoliposome at ambient temperature. It should be also taken into account that the solubilization of membrane proteins in detergents is an alternative means to study structure in solution NMR. However, it is not always able faithfully to mimick the biomembrane environment, because the interface structure is not always the same between the bilayer and detergent system. This typically occurs in the case of PLC-81(1-140) described in Section 4.2.4 and other types of peptide systems. 

A number of studies have taken advantage of the fact that membrane proteins contain one or more tryptophans, the fluorescence of which can be used to determine the conformation of the protein or its position in the membrane.(88 91) Of course, the information is limited by the number of tryptophans and the fact that a tryptophan may not be positioned in the region of the protein of interest. While a single tryptophan often simplifies the situation, most often there are a number in the protein so that it is difficult to extract useful information. 

Carriers consist of proteins that extend completely across the membrane. A solute being transported is initially bonnd to external sites on the carrier protein subsequent changes in the conformation of the protein resnlt in the transfer of the bound solnte across to the other side of the membrane where it dissociates. 

Faraldo-Gomez, J.D., Forrest, L.R., Baaden, M., Bond, P.J., Domene, C., Patargias, G., Cuthbertson, J., Sansom, M.S.P. Conformational sampling and dynamics of membrane proteins from 10-nanosecond computer simulations. Proteins Struct. Funct. Bioinformatics 2004, 57, 783-91. 

New glycolipids have to be synthesized to get further insights into liquid crystal properties (mainly lyotropic liquid crystals), surfactant properties (useful in the extraction of membrane proteins), and factors that govern vesicle formation, stability and tightness. New techniques have to be perfected in order to allow to make precise measurements of thermodynamic and kinetic parameters of binding in 3D-systems and to refine those already avalaible with 2D-arrays. Furthermore, molecular mechanics calculations should also be improved to afford a better modeling of the conformations of carbohydrates at interfaces, in relation with physical measurements such as NMR. 

Available evidence indicates, then, that ORD-CD studies reflect a real property of membrane protein. However, results from different laboratories vary. The lack of agreement may reflect true differences in protein conformation from membrane to membrane, but in some cases the effects observed might be artifacts arising, for example, from different preparative procedures or from some poorly understood property of scattering systems. 

G proteins are another family of membrane proteins believed to modulate mechanochemical transduction pathways. Mechanical stimulation changes the conformation of G protein that leads to growth-factorlike changes that initiate secondary messenger cascades leading to cell growth. It has been reported that cyclic strain of smooth muscle cells significantly decreased steady-state levels of G protein and adenylate cyclase activity. Muscular stimulation also appears to be coupled with G protein activation in small arteries. 

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