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| [[image:2byn.png |left|300px]]
| | <StructureSection load='' size='350' side='right' scene='39/399849/Cv/10' caption='Lymnaea acetylcholine-binding protein pentamer complex with acetylcholine (PDB code [[3wip]])'> |
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| | __TOC__ |
| 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). The crystal structure of the AChBP homopentamer 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.
| | == Function == |
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| | [[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. |
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| == AChBP - Apo proteins ==
| | See also -<br /> |
| | *[[Acetylcholine Receptor and its Reaction to Cobra Venom]]<br //> |
| | *[[Binding site of AChR]]. |
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| [[2w8e]], [[2byn]] – '''''Aplysia californica''''' (AcAChBP) <br />
| | == Structural highlights == |
| [[1ux2]], [[1i9b]] – '''''Lymnaea stagnalis''''' (LsAChBP) <br />
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| [[2bj0]] – '''''Bulinus truncatus'''''
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| == AChBP + marine biotoxins == | | The crystal structures of the ''Lymnaea stagnalis'' <ref>PMID:11357122</ref> and the ''Aplysia californica'' <ref name="Hansen">PMID:16193063</ref> <scene name='39/399849/Cv/11'>AChBP homopentamer</scene> 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. <scene name='39/399849/Cv/12'>The binding site of AChBP is located at the interface of neighboring subunits</scene>. <ref name="Olsen">PMID:24637639</ref> Chain A is in cyan, chain B is in salmon, ACh is in yellow. |
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| [[2wzy]] – AcAChBP + 13-desmethyl spirolide C <br />
| | == Relevance == |
| [[2x00]] - AcAChBP + gymnodimine A <br />
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| == AChBP + partial agonists; Activate the receptor with partial efficacy ==
| | Like the nAChR, AChBP - with ca. 20% sequence similarity - binds agonists and antagonists like ACh <ref name="Olsen">PMID:24637639</ref>, nicotine <ref>PMID:15046723</ref>, α-bungarotoxin <ref>PMID:11683996</ref>, epibatidine <ref name="Hansen">PMID:16193063</ref> 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. |
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| [[2wn9]] - AcAChBP + 4-OH-DMXBA <br />
| | == 3D Structures of Acetylcholine binding protein == |
| [[2wnc]] - AcAChBP + tropisetron <br /> | | [[Acetylcholine binding protein 3D structures]] |
| [[2wnj]] - AcAChBP + DMXBA <br />
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| [[2wnl]] – AcAChBP + anabaseine [ <br />
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| == AChBP+ions; Mimicking the ion conductance of the receptor ==
| | </StructureSection> |
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| [[3gua]] – AcAChBP + sulfate <br />
| | ==Additional Resources== |
| | | For additional information, see: [[Alzheimer's Disease]] |
| == AChBP+ neonicotinoids; Insecticides with lower affinity to mammals ==
| | <br /> |
| | | == References == |
| [[3c79]] - AcAChBP + imidacloprid <br />
| | <references/> |
| [[2zju]] – LsAChBP + imidacloprid <br />
| | [[Category:Topic Page]] |
| [[3c84]] – AcAChBP + thiacloprid <br />
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| [[2zjv]] – LsAChBP+clothianidin <br />
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| == AChBP+ non-competitive inhibitors which bind at site different than the active site and reduce the rate of receptor reaction == | |
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| [[2pjz]] - AcAChBP+cocaine <br />
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| [[2ph9]] - AcAChBP+galanthamine <br />
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| [[2w8f]], [[2w8g]] – AcAChBP + in silico compounds <br />
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| == AChBP+ peptide inhibitors ==
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| [[2c9t]], [[2byp]], [[2br8]] - AcAChBP+conotoxin IMI <br />
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| [[1yi5]] – AcAChBP+cobratoxin <br />
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| == AChBP+ nicotinic agonists enhance the action of the nAChR == | |
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| [[2pgz]] – AcAChBP+cocaine <br />
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| [[2byr]] - AcAChBP+methyllycaconitine <br />
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| [[2bys]] - AcAChBP+lobeline <br /> | |
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| == AChBP+ ligand homologs of the ligand acetylcholine ==
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| [[1uv6]] - LsAChBP+ carbamylcholine <br />
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| [[1uw6]] - LsAChBP+nicotine <br />
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| == AChBP+others ==
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| [[2br7]] – AcAChBP+ HEPES
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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 -
Structural highlights
The crystal structures of the Lymnaea stagnalis [1] and the Aplysia californica [2] AChBP homopentamer 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. The binding site of AChBP is located at the interface of neighboring subunits. [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
- ↑ 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
- ↑ 2.0 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
- ↑ 3.0 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:https://dx.doi.org/10.1371/journal.pone.0091232
- ↑ 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
- ↑ 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
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Additional Resources
For additional information, see: Acetylcholine Receptor and its Reaction to Cobra Venom
References
