Membrane receptor groups

Many proteins found in nature are glycoproteins because they contain covalently linked oligo- and polysaccharide groups. The list of known glycoproteins includes structural proteins, enzymes, membrane receptors, transport proteins, and immunoglobulins, among others. In most cases, the precise function of the bound carbohydrate moiety is not understood. 

Figure 11.1 Schematic representation of iron uptake mechanisms, (a) The transferrin-mediated pathway in animals involves receptor-mediated endocytosis of diferric transferrin (Tf), release of iron at the lower pH of the endocytic vesicle and recycling of apoTf. (b) The mechanism in H. influenzae involves extraction of iron from Tf at outer membrane receptors and transport to the inner membrane permease system by a periplasmic ferric binding protein (Fbp). From Baker, 1997. Reproduced by permission of Nature Publishing Group.

Almost all receptor-mediated neutrophil functions are mediated via GTP-binding proteins (G-proteins), which provide the link between occupancy of plasma membrane receptors and the activation of intracellular enzymes, such as phospholipases and protein kinases. There are two groups of G-proteins those that are heterotrimeric and those with low molecular weight. 

Lipoproteins are classified into five groups. In order of decreasing size and increasing density, these are chylomicrons, VLDLs (very-low-density lipoproteins), IDLs (inter-mediate-density lipoproteins), LDLs (low-density lipoproteins), and HDLs (high-density lipoproteins). The proportions of apoproteins range from 1 % in chylomicrons to over 50% in HDLs. These proteins serve less for solubility purposes, but rather function as recognition molecules for the membrane receptors and enzymes that are involved in lipid exchange. 

In the mid-seventies. Law et al. studying ACTH-(1-39) and fragments, found a transition from random coil to a helix structure when the solvent water was gradually replaced by trifluoroethanol (TFE) (43). This latter solvent had been shown to favour the establishment of ordered structures ( 3-sheet or a-helix) like a membrane-receptor environment ("membrane-receptor mimetic" properties) (47). Subsequent work of the groups of Low and Fermandjian on ACTH-(1-39) and several large fragments and... 

Several groups have demonstrated the use of trNOESY experiments to determine the structure of peptides bound to their receptor. For example, Kisselev et al. determined the 3D solution structure of the transductin a-subunit bound to light-activated rhodopsin (51). They found that the peptide IKENLKDCGLF formed an a-helix terminated by an open reverse turn (Fig. 11), while in contrast the conformation of the peptide remained disordered when in contact with nonactivated rhodopsin. Their findings led to the development of derivatives of the peptide that maintained the binding conformation and had improved affinity (73). Importantly, in their studies they used rhodopsin in a membrane environment (extracted from bovine rods), emphasizing the capabilities of the method for the study of integral membrane receptor directed inhibitors in their natural environment. 

Specific domains of proteins (for example, those mentioned in the section Organic Phase ) adsorbed to biomaterial surfaces interact with select cell membrane receptors (Fig. 8) accessibility of adhesive domains (such as specific amino acid sequences) of select adsorbed proteins may either enhance or inhibit subsequent cell (such as osteoblast) attachment (Schakenraad, 1996). Several studies have provided evidence that properties (such as chemistry, charge, and topography) of biomaterial surfaces dictate select interactions (such as type, concentration, and conformation or bioactivity) of plasma proteins (Sinha and Tuan, 1996 Horbett, 1993 Horbett, 1996 Brunette, 1988 Davies, 1988 Luck et al., 1998 Curtis and Wilkinson, 1997). Albumin has been the protein of choice in protein-adsorption investigations because of availability, low cost (compared to other proteins contained in serum), and, most importantly, well-documented conformation or bioactive structure (Horbett, 1993) recently, however, a number of research groups have started to examine protein (such as fibronectin and vitronectin) interactions with material surfaces that are more pertinent to subsequent cell adhesion (Luck et al., 1998 Degasne et al., 1999 Dalton et al., 1995 Lopes et al., 1999). 

---