ISSN:
1573-4943
Keywords:
Antibody
;
acetylcholine receptor
;
synthetic peptide
;
binding profile
;
exposed regions
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract To study the structural organization of the main extracellular domain of the nicotinic acetylcholine receptor (AChR)α subunit in live muscle cells, we examined the native membrane-bound receptors in cultured mouse skeletal muscle cells for their ability to bind a panel of antibodies against uniform-sized overlapping synthetic peptides which collectively represent this entire domain. The binding profile indicated that the regions α23–49,α78–126,α146–174, andα182–210 are accessible to binding with antibody. Residuesα23–49,α78–126, andα194–210 contain binding regions forα-neurotoxin and some myasthenia gravis autoantibodies. A comparison of this binding profile with the profile obtained for membrane-boundTorpedo californica AChR in isolated membrane fractions showed some similarities as well as significant differences between the subunit organization in the isolated membrane fraction and that in the membrane of live muscle cells. Regionsα89–104 andα158–174, which are exposed in the isolated membrane fraction, are also exposed in the live cell. On the other hand, regionsα23–49, andα182–210, which are exposed in the live cell, are not accessible in the isolated membrane and, furthermore, the regionα1–16, which has marginal accessibility in the cell, becomes highly accessible in the membrane isolates. The exposed regions defined by this study may be the primary targets for the initial autoimmune attack on the receptors in experimental autoimmune myasthenia gravis.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01886954
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