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  • Acetylcholine Receptor  (1)
  • Blood brain barrier  (1)
  • 1
    ISSN: 0948-5023
    Schlagwort(e): Acetylcholine Receptor ; Acetylcholinesterase ; Modeling ; Receptor ; Homology ; 3-D Structure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Acetylcholine is a ligand for both acetylcholinesterases and nicotinic acetylcholine receptors. Hence, at least some local sequence and structural similarities between the acetylcholinesterases and the receptors which recognize acetylcholine (ACh) might be expected. Peterson [2] produced an alignment of the ACh binding region between these two types of ACh–binding molecules, featuring a number of well conserved residues. The extent of this region of sequence similarity suggests the possible existence of a common ancenstral ACh binding module. To attempt to further validate Peterson′s sequence alignment we have built a homology model of the ACh binding domain of the human neuromuscular nicotinic acetylcholine receptor based on the structure of acetylcholinesterase from Torpedo californica. Using this 3–D model we have examined the residues which were previously shown to interact with the endogenous ligand by various methods (mapping, site–directed mutagenesis). The consistency of such data with the model provides further support for a structural similarity and possibly a divergent evolutionary relationship between the ACh–binding domains of these two classes of proteins. Results suggest that this model may be able to contribute to an understanding of the structure and function of the ACh receptor. Using this case as an example, we propose that 3–dimensional computer modeling can be used as a tool to evaluate distant homologies when adequate experimental data (e.g., site–directed mutagenesis) is available.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Journal of comparative physiology 161 (1991), S. 521-524 
    ISSN: 1432-136X
    Schlagwort(e): Transferrin receptors ; Iron transport ; Brain capillaries ; Species specificity ; Blood brain barrier
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The role of specific transferrin (Tf) and Tf receptor interaction on brain capillary endothelial cells in iron transport from the plasma to the brain was investigated by using Tf from several species of animals labeled with 59Fe and 125I, and 15-day and adult rats. The rate of iron transfer was much greater in the 15-day rats. It was greatest with Tf from the mammals, rat, rabbit and human, but much lower with chicken ovotransferrin and quokka (a marsupial), toad, lizard, crocodile, and fish Tf. The uptake of Tf by the brain showed a similar pattern, except for a very high uptake of ovotransferrin (ovo Tf). Iron uptake by the femurs (a source of bone marrow) was also high with Tf from the mammalian species and low with the other types of Tf, but showed little change with aging of the animals. It is concluded that iron transport into the brain is dependent on the function of Tf receptors, probably on capillary endothelial cells, and that these receptors show the same type of species specificity as the receptors on immature erythroid cells. Also, the decrease in iron uptake by the brain as rats age from 15 days to adulthood is specific for the brain and is not a general effect of the aging process.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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