2BR8

Crystal Structure of Acetylcholine-binding Protein (AChBP) from Aplysia californica in complex with an alpha-conotoxin PnIA variant

Summary for 2BR8

• Entry DOI: 10.2210/pdb2br8/pdb
• Related: 1PEN 2BR7
• Descriptor: SOLUBLE ACETYLCHOLINE RECEPTOR, ALPHA-CONOTOXIN PNIA, SULFATE ION, ... (4 entities in total)
• Functional Keywords: receptor/inhibitor, receptor-inhibitor complex, glycoprotein, igg-fold, immunoglobulin domain, pentamer, nicotinic receptor, alpha-conotoxin, receptor, acetylcholine receptor inhibitor, amidation, neurotoxin, postsynaptic neurotoxin, sulfation, toxin
• Biological source: APLYSIA CALIFORNICA (CALIFORNIA SEA HARE); More
• Total number of polymer chains: 10
• Total formula weight: 132333.31

Authors

Celie, P.H.N.,Kasheverov, I.E.,Mordvintsev, D.Y.,Hogg, R.C.,van Nierop, P.,van Elk, R.,van Rossum-Fikkert, S.E.,Zhmak, M.N.,Bertrand, D.,Tsetlin, V.,Sixma, T.K.,Smit, A.B. (deposition date: 2005-05-03, release date: 2005-06-07, Last modification date: 2024-11-06)

Primary citation

Celie, P.H.N.,Kasheverov, I.E.,Mordvintsev, D.Y.,Hogg, R.C.,Van Nierop, P.,Van Elk, R.,Van Rossum-Fikkert, S.E.,Zhmak, M.N.,Bertrand, D.,Tsetlin, V.,Sixma, T.K.,Smit, A.B.
Crystal Structure of Nicotinic Acetylcholine Receptor Homolog Achbp in Complex with an Alpha-Conotoxin Pnia Variant
Nat.Struct.Mol.Biol., 12:582-, 2005

PubMed Abstract: Conotoxins (Ctx) form a large family of peptide toxins from cone snail venoms that act on a broad spectrum of ion channels and receptors. The subgroup alpha-Ctx specifically and selectively binds to subtypes of nicotinic acetylcholine receptors (nAChRs), which are targets for treatment of several neurological disorders. Here we present the structure at a resolution of 2.4 A of alpha-Ctx PnIA (A10L D14K), a potent blocker of the alpha(7)-nAChR, bound with high affinity to acetylcholine binding protein (AChBP), the prototype for the ligand-binding domains of the nAChR superfamily. Alpha-Ctx is buried deep within the ligand-binding site and interacts with residues on both faces of adjacent subunits. The toxin itself does not change conformation, but displaces the C loop of AChBP and induces a rigid-body subunit movement. Knowledge of these contacts could facilitate the rational design of drug leads using the Ctx framework and may lead to compounds with increased receptor subtype selectivity.

PubMed: 15951818
DOI: 10.1038/NSMB951

Experimental method

X-RAY DIFFRACTION (2.4 Å)