PDBsum entry 2c9t

Receptor/toxin

PDB id: 2c9t

Contents

Protein chains

(+ 4 more) 205 a.a. *

(+ 2 more) 13 a.a. *

Waters ×1514

* Residue conservation analysis

PDB id:

2c9t

Name:

Receptor/toxin

Title:

Crystal structure of acetylcholine binding protein (achbp) from aplysia californica in complex with alpha-conotoxin imi

Structure:

Soluble acetylcholine receptor. Chain: a, b, c, d, e, f, g, h, i, j. Synonym: acetylcholine binding protein. Other_details: alpha-conotoxin imi bound in receptor sites. Alpha-conotoxin imi. Chain: k, m, o, p, q, r, s, t. Fragment: residues 5-16. Synonym: alpha-ctx imi. Other_details: alpha-conotoxin imi bound in receptor sites

Source:

Aplysia californica. California sea hare. Organism_taxid: 6500. Conus imperialis. Imperial cone. Organism_taxid: 35631

Biol. unit:

80mer (from PDB file)

Resolution:

2.25Å R-factor: 0.171 R-free: 0.227

Authors:

C.Ulens,R.C.Hogg,P.H.Celie,D.Bertrand,V.Tsetlin,A.B.Smit,T.K.Sixma

Key ref:

C.Ulens et al. (2006). Structural determinants of selective alpha-conotoxin binding to a nicotinic acetylcholine receptor homolog AChBP. Proc Natl Acad Sci U S A, 103, 3615-3620. PubMed id: 16505382 DOI: 10.1073/pnas.0507889103

Date:

14-Dec-05 Release date: 13-Feb-06

Protein chains

Q8WSF8  (Q8WSF8_APLCA) -  Soluble acetylcholine receptor from Aplysia californica

Seq: 236 a.a.

Struc: 205 a.a.*

Protein chains

P50983  (CA1_CONIM) -  Alpha-conotoxin ImI (Fragment) from Conus imperialis

Seq: 17 a.a.

Struc: 13 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1073/pnas.0507889103

Proc Natl Acad Sci U S A 103:3615-3620 (2006)

PubMed id: 16505382

Structural determinants of selective alpha-conotoxin binding to a nicotinic acetylcholine receptor homolog AChBP.

C.Ulens, R.C.Hogg, P.H.Celie, D.Bertrand, V.Tsetlin, A.B.Smit, T.K.Sixma.

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.

Selected figure(s)

Figure 2.
Fig. 2. Crystal structure of -conotoxin ImI bound to Ac-AChBP viewed along the fivefold axis. Conotoxins are in red.

Figure 4.
Fig. 4. Molecular contacts at the toxin–receptor interface. (A and B) Details of molecular contacts between Ac-AChBP and -conotoxin PnIA(A10L D14K) (A) and -conotoxin ImI (B). The conotoxin is shown in red, the principal binding side in yellow, and the complementary binding side in blue. Disulfide bridges are green. Dashed lines indicate H-bonds or salt bridges. (C) Sequence alignment of Ac-AChBP, Ls-AChBP, and [7], [9], [3], [4] nAChRs. Sequence numbering at the top is for Ac-AChBP and at the bottom is for [7] nAChR. Residues of the principal binding side that interact with -conotoxin ImI are shown in yellow; residues of the complementary binding side are in blue. Contacts that are present in the complex with ImI, but not in the complex with PnIA(A10L D14K), are labeled with below the alignment.

Figures were selected by the author.