AchBP crystal structure

Cerlie, T. H., Van-Rossum-Fikkert, S. E., Van Dijk, W. J., Brej, K., Smit, A. B. and Sixma, T. Nicotine and carbamyl-choline binding to nicotinic receptors as studied in AChBP crystal structures. Neuron 41, 907-914, 2004. 

Buisson B, Bertrand D (2001) Chronic exposure to nicotine upregulates the human alpha4beta2 nicotinic acetylcholine receptor function. J Neurosci 21 1819-1829 CeUe PH, van Rossum-Fikkert SE, van Dijk WJ, Brejc K, Smit AB, Sixma TK (2004) Nicotine and carbamylcholine binding to nicotinic acetylcholine receptors as studied in AChBP crystal structures. Neuron 41 907-914... 

Celie PH et al Nicotine and carbamylcholine binding to nicotinic acetylcholine receptors as studied in AChBP crystal structures. Neuron 2004 41 907. [PMID 15046723]... 

Fig. 4. (A) 5-HTj homology model based on the AChBP crystal structure (1I9B) showing the binding loops within two of the five subunits that make up the extracellular domain of the 5-HT3 receptor. The binding site is formed from loops A-C within the principal subunit and loops D-F in the complementary subunit. (B) Locations of the amino acids that are proposed to be within 5 A of the ligand-binding site.

The role of loop F residues have yet to be elucidated. In the AChBP crystal structure, the loop F region was poorly resolved (19) thus, its current location on the homology model on the 5-HT3 receptor is only tentative. We await further studies to reveal the importance of this region. 

A more precise description of the extended conformational change, linking to the transmembrane portion, has recently been derived by comparing the 4.6-A structure of the extracellular domain with the crystal structure of the AChBP. It is found that, to a good approximation, there are two alternative extended conformations of the receptor subunits (one characteristic of either a subunit before activation, and the other characteristic of the... 

Whenever it has not been possible to obtain crystals of any nAChR of sufficient quality for high-resolution X-ray crystallography, both the crystal structure of a soluble homopentameric AChBP and the refined model of the membrane-associated Torpedo AChR [98], based on the crystal structure of AChBP, can support the understanding of the ligand-receptor interactions considerably. 

The crystal structure of AChBP from the water snail Lymnaea stagnalis (Ls) was determined recently, in complex with DHpE. The structure reveals that binding of DHPE to this AChBP imposes closure of the C-loop as is the case with agonists, but also a shift perpendicular to previously observed C-loop movements. These observations suggest that DHpE may antagonize the receptor via a different mechanism compared to prototypical antagonists and toxins [68],... 

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