Acetylcholine binding protein

From Proteopedia

spinqualitylabelsall models Lymnaea acetylcholine-binding protein pentamer complex with acetylcholine (PDB code 3wip) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Structural highlights 3 Relevance 4 3D Structures of Acetylcholine binding protein Function Acetylcholine binding protein (AChBP) is secreted by snails into cholinergic synapses, where it modulates transmission by binding acetylcholine (ACh). Sequence alignment revealed high similarity to the extracellular domains of the ligand-binding subunits of the nicotinic acetylcholine receptor (nAChR). AChBP alpha7 is highly similar to the ligand-binding domain of nAChR alpha7. See also - Acetylcholine Receptor and its Reaction to Cobra Venom Binding site of AChR. Structural highlights The crystal structures of the Lymnaea stagnalis [1] and the Aplysia californica [2] indeed provides a valuable model for identifying the nature of the ligand-binding domains and of the subunit interfaces of the nAChR. Furthermore, crystal structures of complexes of AChBP with various agonists and antagonists have provided detailed insight into the neurotransmitter binding site of nAChRs. . [3] Chain A is in cyan, chain B is in salmon, ACh is in yellow. Relevance Like the nAChR, AChBP - with ca. 20% sequence similarity - binds agonists and antagonists like ACh [3], nicotine [4], α-bungarotoxin [5], epibatidine [2] with similar affinities hence it is a useful tool for understanding nAChR activity. Both receptors contain a Cys-Cys loop at the subunits interface as well as conserved residues at the ACh binding site. 3D Structures of Acetylcholine binding protein Acetylcholine binding protein 3D structures

Additional Resources

For additional information, see: Alzheimer's Disease

References

1. ↑ Brejc K, van Dijk WJ, Klaassen RV, Schuurmans M, van Der Oost J, Smit AB, Sixma TK. Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors. Nature. 2001 May 17;411(6835):269-76. PMID:11357122 doi:10.1038/35077011
2. ↑ ^{2.0 2.1} Hansen SB, Sulzenbacher G, Huxford T, Marchot P, Taylor P, Bourne Y. Structures of Aplysia AChBP complexes with nicotinic agonists and antagonists reveal distinctive binding interfaces and conformations. EMBO J. 2005 Oct 19;24(20):3635-46. Epub 2005 Sep 29. PMID:16193063
3. ↑ ^{3.0 3.1} Olsen JA, Balle T, Gajhede M, Ahring PK, Kastrup JS. Molecular recognition of the neurotransmitter acetylcholine by an acetylcholine binding protein reveals determinants of binding to nicotinic acetylcholine receptors. PLoS One. 2014 Mar 17;9(3):e91232. doi: 10.1371/journal.pone.0091232. eCollection, 2014. PMID:24637639 doi:http://dx.doi.org/10.1371/journal.pone.0091232
4. ↑ Celie PH, van Rossum-Fikkert SE, van Dijk WJ, Brejc K, Smit AB, Sixma TK. Nicotine and carbamylcholine binding to nicotinic acetylcholine receptors as studied in AChBP crystal structures. Neuron. 2004 Mar 25;41(6):907-14. PMID:15046723
5. ↑ Harel M, Kasher R, Nicolas A, Guss JM, Balass M, Fridkin M, Smit AB, Brejc K, Sixma TK, Katchalski-Katzir E, Sussman JL, Fuchs S. The binding site of acetylcholine receptor as visualized in the X-Ray structure of a complex between alpha-bungarotoxin and a mimotope peptide. Neuron. 2001 Oct 25;32(2):265-75. PMID:11683996