| Autor: |
Gleitsman KR; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA., Kedrowski SM, Lester HA, Dougherty DA |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of biological chemistry [J Biol Chem] 2008 Dec 19; Vol. 283 (51), pp. 35638-43. Date of Electronic Publication: 2008 Oct 24. |
| DOI: |
10.1074/jbc.M807226200 |
| Abstrakt: |
The muscle nicotinic acetylcholine receptor is a large, allosteric, ligand-gated ion channel with the subunit composition alpha2betagammadelta. Although much is now known about the structure of the binding site, relatively little is understood about how the binding event is communicated to the channel gate, causing the pore to open. Here we identify a key hydrogen bond near the binding site that is involved in the gating pathway. Using mutant cycle analysis with the novel unnatural residue alpha-hydroxyserine, we find that the backbone N-H of alphaSer-191 in loop C makes a hydrogen bond to an anionic side chain of the complementary subunit upon agonist binding. However, the anionic partner is not the glutamate predicted by the crystal structures of the homologous acetylcholine-binding protein. Instead, the hydrogen-bonding partner is the extensively researched aspartate gammaAsp-174/deltaAsp-180, which had originally been identified as a key binding residue for cationic agonists. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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