Crystal Structure of Lymnaea stagnalis AChBP Complexed with the Potent nAChR Antagonist DHßE Suggests a Unique Mode of Antagonism

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Crystal Structure of Lymnaea stagnalis AChBP Complexed with the Potent nAChR Antagonist DHßE Suggests a Unique Mode of Antagonism. / Shahsavar, Azadeh; Kastrup, Jette S; Nielsen, Elsebet Ø.; Kristensen, Jesper L; Gajhede, Michael; Balle, Thomas.

In: P L o S One, Vol. 7, No. 8, 2012, p. e40757.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Shahsavar, A, Kastrup, JS, Nielsen, EØ, Kristensen, JL, Gajhede, M & Balle, T 2012, 'Crystal Structure of Lymnaea stagnalis AChBP Complexed with the Potent nAChR Antagonist DHßE Suggests a Unique Mode of Antagonism', P L o S One, vol. 7, no. 8, pp. e40757. https://doi.org/10.1371/journal.pone.0040757

APA

Shahsavar, A., Kastrup, J. S., Nielsen, E. Ø., Kristensen, J. L., Gajhede, M., & Balle, T. (2012). Crystal Structure of Lymnaea stagnalis AChBP Complexed with the Potent nAChR Antagonist DHßE Suggests a Unique Mode of Antagonism. P L o S One, 7(8), e40757. https://doi.org/10.1371/journal.pone.0040757

Vancouver

Shahsavar A, Kastrup JS, Nielsen EØ, Kristensen JL, Gajhede M, Balle T. Crystal Structure of Lymnaea stagnalis AChBP Complexed with the Potent nAChR Antagonist DHßE Suggests a Unique Mode of Antagonism. P L o S One. 2012;7(8):e40757. https://doi.org/10.1371/journal.pone.0040757

Author

Shahsavar, Azadeh ; Kastrup, Jette S ; Nielsen, Elsebet Ø. ; Kristensen, Jesper L ; Gajhede, Michael ; Balle, Thomas. / Crystal Structure of Lymnaea stagnalis AChBP Complexed with the Potent nAChR Antagonist DHßE Suggests a Unique Mode of Antagonism. In: P L o S One. 2012 ; Vol. 7, No. 8. pp. e40757.

Bibtex

@article{d0e76e5e3b19481aad7bafc4826c6c10,
title = "Crystal Structure of Lymnaea stagnalis AChBP Complexed with the Potent nAChR Antagonist DH{\ss}E Suggests a Unique Mode of Antagonism",
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-{\ss}-erythroidine (DH{\ss}E), which is a potent competitive antagonist of nAChRs. The structure reveals that binding of DH{\ss}E 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 DH{\ss}E may antagonize the receptor via a different mechanism compared to prototypical antagonists and toxins.",
author = "Azadeh Shahsavar and Kastrup, {Jette S} and Nielsen, {Elsebet {\O}.} and Kristensen, {Jesper L} and Michael Gajhede and Thomas Balle",
year = "2012",
doi = "10.1371/journal.pone.0040757",
language = "English",
volume = "7",
pages = "e40757",
journal = "P L o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "8",

}

RIS

TY - JOUR

T1 - Crystal Structure of Lymnaea stagnalis AChBP Complexed with the Potent nAChR Antagonist DHßE Suggests a Unique Mode of Antagonism

AU - Shahsavar, Azadeh

AU - Kastrup, Jette S

AU - Nielsen, Elsebet Ø.

AU - Kristensen, Jesper L

AU - Gajhede, Michael

AU - Balle, Thomas

PY - 2012

Y1 - 2012

N2 - 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-ß-erythroidine (DHßE), which is a potent competitive antagonist of nAChRs. The structure reveals that binding of DHßE 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 DHßE may antagonize the receptor via a different mechanism compared to prototypical antagonists and toxins.

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

U2 - 10.1371/journal.pone.0040757

DO - 10.1371/journal.pone.0040757

M3 - Journal article

C2 - 22927902

VL - 7

SP - e40757

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 8

ER -

ID: 40766378