4alx

Publication Abstract from PubMed

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that belong to the Cys-loop receptor superfamily. These receptors are allosteric proteins that exist in different conformational states, including resting (closed), activated (open), and desensitized (closed) states. The acetylcholine binding protein (AChBP) is a structural homologue of the extracellular ligand-binding domain of nAChRs. In previous studies, the degree of the C-loop radial extension of AChBP has been assigned to different conformational states of nAChRs. It has been suggested that a closed C-loop is preferred for the active conformation of nAChRs in complex with agonists whereas an open C-loop reflects an antagonist-bound (closed) state. In this work, we have determined the crystal structure of AChBP from the water snail Lymnaea stagnalis (Ls) in complex with dihydro-beta-erythroidine (DHbetaE), which is a potent competitive antagonist of nAChRs. The structure reveals that binding of DHbetaE to AChBP imposes closure of the C-loop as agonists, but also a shift perpendicular to previously observed C-loop movements. These observations suggest that DHbetaE may antagonize the receptor via a different mechanism compared to prototypical antagonists and toxins.

Crystal Structure of Lymnaea stagnalis AChBP Complexed with the Potent nAChR Antagonist DHbetaE Suggests a Unique Mode of Antagonism.,Shahsavar A, Kastrup JS, Nielsen EO, Kristensen JL, Gajhede M, Balle T PLoS One. 2012;7(8):e40757. Epub 2012 Aug 22. PMID:22927902^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.