ROLE OF CHOLESTEROL AS A STRUCTURAL AND FUNCTIONAL EFFECTOR OF THE NICOTINIC ACETYLCHOLINE-RECEPTOR
ROLE OF CHOLESTEROL AS A STRUCTURAL AND FUNCTIONAL EFFECTOR OF THE NICOTINIC ACETYLCHOLINE-RECEPTOR
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DOI：
10.1042/bst0220776
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发表时间：
1994-08-01
影响因子：
3.9
通讯作者：
GONZALEZROS, JM
中科院分区：
文献类型：
--
作者：
FERNANDEZBALLESTER, G;CASTRESANA, J;GONZALEZROS, JM
The nicotinic acetylcholine receptor (AcChR) from zyxwvutsrqponmlkji Torpedo is a transmembrane glycoprotein composed of four different polypeptide subunits zyxwvutsrqponmlkjih (a, zyxwvutsrqponmlk p, y and 6) in a 2: 1: 1: 1 stoichiometry [1-31, Binding of cholinergic agonists to sites on extracellular domains of the AcChR elicits the formation of a transient cation channel within the protein, which is responsible for the initiation of postsynaptic membrane depolarization. On continuous exposure to the agonist, however, the channel opening response becomes blocked and the affinity for the agonists increases, a process known as desensitization [4]. Keconstitution of the purified AcChR protein into artificial liposomes of defined composition has shown that the presence of certain lipids in the reconstituted samples, namely cholesterol and acidic phospholipids, is important in preserving the ability of the reconstituted AcChR to exhibit an optimal cation channel activity [1, s-lo]. Nevertheless, in spite of the existing information on the lipid dependence of AcChR function, very little is known about the molecular basis of such phenomena. In this paper, we have used the conformational sensitivity of the amide I band in the ir spectrum of the purified AcChR protein reconstituted into lipid vesicles to explore the possibility that cholesterol causes changes in the protein structure that might be responsible for the observed alteration in AcChR function. Fourier-transform ir (Ftir) spectroscopic methods have shown great potential for detecting structural differences between the various possible conformers of complex membrane proteins [11-14], including the AcChR [15-201. This information is summarized in Table 1, along with rapid kinetics data of cholinergic agonist-induced cation translocation, to illustrate the functional status of the AcChR in the different reconstituted hilayers.
