2BR8

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.201 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Crystal Structure of Nicotinic Acetylcholine Receptor Homolog Achbp in Complex with an Alpha-Conotoxin Pnia Variant

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.

(2005) Nat Struct Mol Biol 12: 582

  • DOI: https://doi.org/10.1038/nsmb951
  • Primary Citation of Related Structures:  
    2BR7, 2BR8

  • 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.


  • Organizational Affiliation

    Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
SOLUBLE ACETYLCHOLINE RECEPTOR
A, B, C, D, E
217Aplysia californicaMutation(s): 0 
UniProt
Find proteins for Q8WSF8 (Aplysia californica)
Explore Q8WSF8 
Go to UniProtKB:  Q8WSF8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8WSF8
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
ALPHA-CONOTOXIN PNIA
F, G, H, I, J
17Conus pennaceusMutation(s): 2 
UniProt
Find proteins for P50984 (Conus pennaceus)
Explore P50984 
Go to UniProtKB:  P50984
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP50984
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.201 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 67.473α = 90
b = 80.085β = 93.2
c = 134.043γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2005-06-07
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description