2C9T

Crystal Structure Of Acetylcholine Binding Protein (AChBP) From Aplysia Californica In Complex With alpha-Conotoxin ImI

Summary for 2C9T

• Entry DOI: 10.2210/pdb2c9t/pdb
• Related: 1CNL 1E74 1E75 1E76 1G2G 1IM1 1IMI 2BR7 2BR8 2BYN 2BYP 2BYQ 2BYR 2BYS
• Descriptor: SOLUBLE ACETYLCHOLINE RECEPTOR, ALPHA-CONOTOXIN IMI (3 entities in total)
• Functional Keywords: receptor/toxin, receptor-toxin complex, acetylcholine binding protein, nicotinic acetylcholine receptor-toxin complex, conformational flexibility, conotoxin, acetylcholine receptor inhibitor, amidation, neurotoxin, postsynaptic neurotoxin, toxin
• Biological source: APLYSIA CALIFORNICA (CALIFORNIA SEA HARE); More
• Total number of polymer chains: 18
• Total formula weight: 257738.59

Authors

Ulens, C.,Hogg, R.C.,Celie, P.H.,Bertrand, D.,Tsetlin, V.,Smit, A.B.,Sixma, T.K. (deposition date: 2005-12-14, release date: 2006-02-13, Last modification date: 2023-12-13)

Primary citation

Ulens, C.,Hogg, R.C.,Celie, P.H.,Bertrand, D.,Tsetlin, V.,Smit, A.B.,Sixma, T.K.
Structural Determinants of Selective {Alpha}-Conotoxin Binding to a Nicotinic Acetylcholine Receptor Homolog Achbp.
Proc.Natl.Acad.Sci.USA, 103:3615-, 2006

PubMed Abstract: The nicotinic acetylcholine receptor (nAChR) is the prototype member of the superfamily of pentameric ligand-gated ion channels. How the extracellular ligand-binding domain coordinates selective binding of ligand molecules to different subtypes of the receptor is unknown at the structural level. Here, we present the 2.2-A crystal structure of a homolog of the ligand-binding domain of the nAChR, Aplysia californica AChBP (Ac-AChBP), in complex with alpha-conotoxin ImI. This conotoxin is unique in its selectivity toward the neuronal alpha3beta2 and alpha7 nAChR, a feature that is reflected in its selective binding to Ac-AChBP compared with other AChBP homologs. We observe a network of interactions between the residues of the ligand-binding site and the toxin, in which ImI Arg-7 and Trp-10 play a key role. The toxin also forms interactions in the ligand-binding site that were not seen in the complex of Ac-AChBP with PnIA(A10L D14K), a conotoxin variant that lacks binding selectivity to AChBP homologs. In combination with electrophysiological recordings obtained by using the wild-type alpha7 nAChR and L247T mutant, we show that conotoxin ImI inhibits ion conduction by stabilizing the receptor in a desensitized conformation. Comparison of the Ac-AChBP-ImI crystal structure with existing AChBP structures offers structural insight into the extent of flexibility of the interface loops and how their movement may couple ligand binding to channel gating in the context of a nAChR.

PubMed: 16505382
DOI: 10.1073/PNAS.0507889103

Experimental method

X-RAY DIFFRACTION (2.25 Å)