4ALX

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

Summary for 4ALX

• Entry DOI: 10.2210/pdb4alx/pdb
• Related: 1I9B 1UV6 1UW6 1UX2
• Descriptor: ACETYLCHOLINE BINDING PROTEIN, (4bS,6S)-6-methoxy-1,4,6,7,9,10,12,13-octahydro-3H,5H-pyrano[4',3':3,4]pyrido[2,1-i]indol-3-one, PENTAETHYLENE GLYCOL, ... (5 entities in total)
• Functional Keywords: acetylcholine-binding protein, lymnaea stagnalis, dihydro-b-erythroidine, antagonist, c-loop
• Biological source: LYMNAEA STAGNALIS (GREAT POND SNAIL)
• Cellular location: Secreted: P58154
• Total number of polymer chains: 10
• Total formula weight: 265202.04

Authors

Shahsavar, A.,Kastrup, J.S.,Nielsen, E.O.,Kristensen, J.L.,Gajhede, M.,Balle, T. (deposition date: 2012-03-06, release date: 2012-08-29, Last modification date: 2024-10-23)

Primary citation

Shahsavar, A.,Kastrup, J.S.,Nielsen, E.O.,Kristensen, J.L.,Gajhede, M.,Balle, T.
Crystal Structure of Lymnaea Stagnalis Achbp Complexed with the Potent Nachr Antagonist Dh-Betab-E Suggests a Unique Mode of Antagonism
Plos One, 7:40757-, 2012

PubMed 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-β-erythroidine (DHβE), which is a potent competitive antagonist of nAChRs. The structure reveals that binding of DHβE 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 DHβE may antagonize the receptor via a different mechanism compared to prototypical antagonists and toxins.

PubMed: 22927902
DOI: 10.1371/JOURNAL.PONE.0040757

Experimental method

X-RAY DIFFRACTION (2.3 Å)