4ALX: Crystal Structure of Ls-AChBP complexed with the potent nAChR antagonist DHbE

Citation:
Abstract
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.
PDB ID: 4ALXDownload
MMDB ID: 102393
PDB Deposition Date: 2012/3/6
Updated in MMDB: 2012/09
Experimental Method:
x-ray diffraction
Resolution: 2.3  Å
Source Organism:
Similar Structures:
Biological Unit for 4ALX: pentameric; determined by author and by software (PISA)
Molecular Components in 4ALX
Label Count Molecule
Proteins (5 molecules)
5
Acetylcholine Binding Protein
Molecule annotation
Chemicals (14 molecules)
1
5
2
4
3
5
* Click molecule labels to explore molecular sequence information.

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