Extracellular surfaces

FIGURE 9.32 Proteoglycans serve a variety of functions on the cytoplasmic and extracellular surfaces of the plasma membrane. Many of these functions appear to involve the binding of specific proteins to the glycosaminoglycan groups. 

FIGURE 10.8 A schematic diagram of the Na, K -ATPase in mammalian plasma membrane. ATP hydrolysis occurs on the cytoplasmic side of the membrane, Na ions are transported out of the cell, and ions are transported in. The transport stoichiometry is 3 Na out and 2 in per ATP hydrolyzed. The specific inhibitor ouabain (Figure 7.12) and other cardiac glycosides inhibit Na, K -ATPase by binding on the extracellular surface of the pump protein. 

Figure 41-13. Stoichiometry of the Na+-K ATPase pump. This pump moves three Na ions from inside the cell to the outside and brings two K+ ions from the outside to the inside for every molecule of ATP hydrolyzed to ADP by the membrane-associated ATPase. Ouabain and other cardiac glycosides inhibit this pump by acting on the extracellular surface of the membrane. (Courtesy of R Post.)...

The saxitoxins function by binding to a site on the extracellular surface of the voltage-activated sodium channel, interrupting the passive inward flux of sodium ions that would normally occur through the channel while it is in a conducting... 

Exactly how this transporter carries noradrenaline across the neuronal membrane is not known but one popular model proposes that it can exist in two interchangeable states. Binding of Na+ and noradrenaline to a domain on its extracellular surface could trigger a conformation change that results in the sequential opening of outer and inner channel gates on the transporter. This process enables the translocation of noradrenaline from the extracellular space towards the neuronal cytosol. 

Kinetic experiments have shown that phloretin binds asymmetrically to the glucose transporter [37]. However, unlike cytochalasin B it binds exclusively to the extracellular surface of the membrane. Similar asymmetries of binding have been reported for a number of steroids that inhibit glucose transport [38]. For example, androsten-4-ene-3,17-dione (Fig. 1) which inhibits with a K of about 20/rM, binds almost exclusively at the inner surface of the membrane. 

Using these equations, Lowe and Walmsley [48] have calculated the dissociation constants for sugar binding at the extracellular surface of the membrane (K s = b a in Fig. 2) and at the cytoplasmic surface (K. = elf = bid) x [dgich]) from the estimated rate constants for carrier re-orientation and the measured Michaelis constants. The dissociation constant for binding at the extracellular surface of the membrane, calculated in this way, is approximately lOmM and is largely unaffec-... 

Shi et al.71 have assigned the backbone and side-chain chemical shifts for 103 of 238 residues of proteorhodopsin using solid state NMR spectroscopy. Analysis of the chemical shifts has allowed determination of protonation states of several carboxylic acids as well as boundaries and distortions of trans-membrane a-helices and secondary structure elements in the loops. It has been shown that internal Asp227, making a part of the counterion, is ionised, while Glul42 located close to the extracellular surface is neutral. 

In the CNS of mammals, two proteins are needed to accomplish the dual role of adhesion at both myelin bilayer surfaces that P0 effects in the PNS. The four-trans-membrane-domain proteolipid protein (PLP) is likely to be responsible for adhesion of the extracellular surfaces, while the very basic cytoplasmic myelin basic protein... 

Many different receptor types are coupled to G proteins, including receptors for norepinephrine and epinephrine (a- and p-adrenoceptors), 5-hydroxytrypta-mine (serotonin or 5-HT receptors), and muscarinic acetylcholine receptors. Figure 2.1 presents the structure of one of these, the uz-adrenoceptor from the human kidney. All members of this family of G protein-coupled receptors are characterized by having seven membrane-enclosed domains plus extracellular and intracellular loops. The specific binding sites for agonists occur at the extracellular surface, while the interaction with G proteins occurs with the intracellular portions of the receptor. The general term for any chain of events initiated by receptor activation is signal transduction. 

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