Protein transport function

Some of these are listed in Table 46-9 the majority affect lysosomal function. A number of other mutations affecting intracellular protein transport have been reported but are not included here. 

Albumin is the most abundant (about 55%) of the plasma proteins. An important function of albumin is to bind with various molecules in the blood and serve as a carrier protein, transporting these substances throughout the circulation. Substances that bind with albumin include hormones amino acids fatty acids bile salts and vitamins. Albumin also serves as an osmotic regulator. Because capillary walls are impermeable to plasma proteins, these molecules exert a powerful osmotic force on water in the blood. In fact, the plasma colloid osmotic pressure exerted by plasma proteins is the only force that retains water within the vascular compartment and therefore maintains blood volume (see Chapter 15). Albumin is synthesized in the liver. 

Kam, N.W.S. and Dai, H.J. (2005) Carbon nanotubes as intracellular protein transporters generality and biological functionality. Journal of the American Chemical Society, 127 (16), 6021-6026. Heller, D.A. et al. (2005) Single-walled carbon nanotube spectroscopy in live cells towards long-term labels and optical sensors. Advanced Materials, 17 (23), 2793-2799. 

The other major class of extracellular LBPs of mammals is the lipocalins (Flower, 1996). These are approximately 20 kDa, P-sheet-rich proteins, performing functions such as the transport of retinol in plasma or milk, the capture of odorants in olfaction, invertebrate coloration, dispersal of pheromones, and solubilizing the lipids in tears (Flower, 1996). The retinol-binding protein (RBP) of human plasma is found in association with a larger protein, transthyretin, the complex being larger than the kidney threshold and thus not excreted, although the RBP itself may dissociate from the complex to interact with cell surface receptors in the delivery of retinol (Papiz et al., 1986 Sundaram et al., 1998). 

Figure 12.2 Copper chaperone function, (a) Copper homeostasis in Enterococcus hirae is affected by the proteins encoded by the cop operon. CopA, Cu1+-import ATPase CopB, Cu1+-export ATPase CopY, Cu1+-responsive repressor copZ, chaperone for Cu1+ delivery to CopY. (b) The CTR family of proteins transports copper into yeast cells. Atxlp delivers copper to the CPx-type ATPases located in the post Golgi apparatus for the maturation of Fet3p. (c) Coxl7p delivers copper to the mitochondrial intermembrane space for incorporation into cytochrome c oxidase (CCO). (d) hCTR, a human homologue of CTR, mediates copper-ion uptake into human cells. CCS delivers copper to cytoplasmic Cu/Zn superoxide dismutase (SOD1). Abbreviations IMM, inner mitochondrial membrane OMM, outer mitochondrial membrane PM, plasma membrane PGV, post Golgi vessel. Reprinted from Harrison et al., 2000. Copyright (2000), with permission from Elsevier Science.

Genes regulated by Fur code for proteins that function in iron transport and iron metabolism under aerobic conditions, iron metabolism is associated with oxidative stress. In addition, some virulence factors are regulated by Fur. Table 3.2 lists examples and functions of Fur- and iron-regulated genes in E. coli, including pathogenic E. coli strains. 

Paiacin, M. A new family of proteins (rBAT and 4F2hc) involved in cationic and zwitterionic amino add transport a tale of two proteins in search of a transport function. /. Exp. Biol. 1994, 396, 123-137. 

Modified mammalian cell systems for the study of the role of transporters and/or metabolism in oral absorption consists of two main components the cell line and the vector bearing a cDNA encoding the protein of interest. The cell line serves two roles first, to support adequate expression of the cDNA and second, to provide a barrier function which is generally critical in assays for transporter function. 

The presence of serum-binding proteins. Some biopharmaceuticals (including insulin-like growth factor (IGF), GH and certain cytokines) are notable in that the blood contains proteins that specifically bind them. Such binding proteins can function naturally as transporters or activators, and binding can affect characteristics such as serum elimination rates. 

The copper transport function of ceruloplasmin has been documented in several reviews (e.g. see refs. 15, 42, 43) and a transport function established. The turnover of ceruloplasmin allows copper ions to move from the major sites of ceruloplasmin synthesis in liver cells [44,45] to peripheral tissues for incorporation into copper-dependent enzymes [46,47], but transport mechanisms may also be active which involve copper atoms in the intact protein. However, the complexity of the protein has made it difficult to determine which, if any, of the six integral copper atoms are involved in copper delivery or whether there exist additional... 

The existence of two distinct functions within the one membrane protein raises a number of interesting questions about transporter functions, such as what is the relative importance of the two functions Can they be allosterically regulated under physiological conditions or manipulated by pharmacological methods What is the structural basis for the dual functions In the next section, we shall attempt to address some of these issues and also to present some of the current understanding of the structural basis for these functional states. 

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