Membrane transport designer proteins

In the absence of steroid hormones the receptors remain in an inactive complex, designated the apo-receptor complex (review Pratt, 1993 Bohen, 1995). In the apore-ceptor complex the receptor is boimd to proteins belonging to the chaperone class. Chaperones are proteins whose levels are increased as a result of a stress situation, such as a rise in ambient temperature. The chaperones assume a central function in the folding process of proteins in the cell. Chaperones aid proteins in avoiding incorrectly folded states. They participate in the folding of proteins during and after ribosomal protein biosynthesis, during membrane transport of proteins, as well as in the correct assembly of protein complexes. 

Resistance to quinolones by efflux has been described in Staph, aureus and Proteus mirabilis. This gene has been designated nor A in Staph, aureus and is homologous to membrane transport proteins coupled to the electromotive force. These proteins have the ability to remove small amounts of quinolone from cells normally and nor A may have arisen as a result of mutations under selective pressure from quinolone use, resulting in a transport protein with increased affinity for these agents. 

When the new term permease was coined to designate bacterial membrane proteins specialized in the transport of specific metabolites [1,2], it covered a concept which was not quite new. The existence of membrane transport systems had been demonstrated in animal tissues by Cori as early as 1925 (see [3]). However, the discovery and characterization of permeases in bacteria revolutionized prospects for studying the properties of transport systems, opening the way to a new field and a very fruitful methodology. 

The term blood-brain barrier (BBB) refers to the special obstacle that drugs encounter when trying to enter the brain from the circulatory system. The difference between the brain and other tissues and organs is that the capillaries in the brain do not have pores for the free flow of small molecules in the interstitial fluid of the brain. To enter the interstitial fluid, all molecules must cross a membrane. This design is a protective measure to defend the brain from unwanted and potentially hazardous xenobiotics. Traditionally, drugs that target the brain or central nervous system (CNS) cross the BBB by passive diffusion. Transport by carrier proteins across the BBB is becoming better understood but remains an area of active research. 

In order for a metal ion to reach its intracellular protein target, a number of complex barriers must be crossed. First, the metal existing in the extracellular environment must traverse the plasma membrane of the cell. The lipid bilayers of cellular membranes are generally impermeable to metals and cellular uptake of the ion requires the action of metal transport proteins. A host of membrane transporters reside at the cell surface, some of which are specific for certain ions (e.g. only copper or only zinc), while others are more promiscuous in their choice of metal ion substrate (e.g. can transport both copper and zinc). But all are designed to ensure that cells acquire proper levels of the essential heavy metal ions such as copper, zinc, iron, and manganese. 

Although several proteins have been designated as plasma membrane transport proteins in mammalian cells, most evidence supports the proposal that only three, FAT/CD36, FATP, and... 

Special proteins, the membrane transport proteins, are responsible for moving the ions across cell membranes. Generally, each protein is designed to transport a particular class of ions. These proteins form a continuous protein pathway across the membrane and therefore allow the ion to migrate across the membrane without coming into direct contact with the hydrophobic interior of the membrane. There are two major classes of membrane transport proteins the carrier proteins and channel proteins. 

The first clue that dissociation of SNARE complexes required the assistance of other proteins came from in vitro transport reactions depleted of certain cytosolic proteins. The observed accumulation of vesicles in these reactions indicated that vesicles could form but were unable to fuse with a target membrane. Eventually two proteins, designated NSF and a-SNAP, were found to be required for ongoing vesicle fusion in the in vitro transport reaction. The function of NSF in vivo can be blocked selectively by N-ethylmaleimide (NEM), a chemical that reacts with an essential -SH group on NSF (hence the name, AlEM-sensitive /actor). 

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