Binding site of AChR: Difference between revisions

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Ma Zhuang, Zicheng Ye, Michal Harel, Angel Herraez, Alexander Berchansky

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 In nAChR, the ligand-binding site is located at the interface between two subunits. The homopentameric α7 receptor contains five identical ligand binding sites. In these sites acrtylcholine is expected to bind through [http://en.wikipedia.org/wiki/Cation%E2%80%93pi_interaction cation-π interactions], where the positive charge of the quaternary ammonium of acetylcholine interacts with the electron-rich aromatic side chains.<ref>PMID:11357122</ref> <scene name='68/688431/Hepes_five_subunits/2'>HEPES</scene> can be refined in the current AChBP structure, it does not make any specific hydrogen bonds with the protein, it stacks with its quaternary ammonium onto <scene name='68/688431/Hepes_trp143/1'>Trp 143</scene> making cation-π interactions as expected for nicotinic agonists.<ref>PMID:11357122</ref> The superimposed model of AChBP and α-BTX suggests that the putative agonist HEPES seen in the AChBP structure is blocked from entering or leaving the AChBP interface cleft by the insertion of <scene name='68/688431/Hepes_black_loop_2/1'>loop 2</scene> of α-BTX into that cleft. This clarifies and explains the strong inhibition of AChR function by the toxin.<ref>PMID:11683996</ref>
-The 13-mer HAP assumes an antiparallel β hairpin structure,  and is held snugly between <scene name='68/688431/Fingers_of_btx/1'>fingers 1,2 and 4</scene> of α-BTX. The shortest and most numerous interactions are formed with finger 2 of α-BTX. The intermolecular interaction between finger2 and two arms of the HAP hairpin make the complex stable, like <scene name='68/688431/188arg_and_39val/1'>Arg188 and Val 39</scene>.
+The 13-mer <scene name='68/688431/Hap/2'>HAP</scene> assumes an antiparallel β hairpin structure. It is held snugly between <scene name='68/688431/Figure_1234/3'>fingers 1,2 and 4</scene> of α-BTX. The shortest and most numerous interactions are formed with <scene name='68/688431/Figure_1234/2'>finger 2</scene> of α-BTX. The two arms of the HAP hairpin assume a β sheet conformation, with residues <scene name='68/688431/Residues_between_btx_and_hap/2'>Leu 2(188 in AChR)-Tyr 4(190 in AChR ) making an intermolecular interaction with α-BTX residues Val39-Glu41</scene> Leu 2(188 in AChR)-Tyr 4(190 in AChR ) making an intermolecular interaction with α-BTX residues Val39-Glu41 on finger 2.
-Affinity labeling experiments which indentified position 10 and 33 of -neurotoxin to be with in 11.5-15.5 Å from AChR residues Cys192-Cys193(Michalet et al ., 2000) agree with the α-BTX-HAP structure where the corresponding Cα distance are 11.05 Å(Pro10-Ser193), 12.72 Å(Cys33-Ser193), 14.45 Å（Pro10-Ser 192）,9.76 Å(Cys33-Ser192),respectively.<ref>PMID:11683996</ref>So through the complex of α-BTX-HAP, we can see the structure of Acetylcholine binding site.