title: Solution conformation of alphaA-conotoxin EIVA, a potent neuromuscular nicotinic acetylcholine receptor antagonist from Conus ermineus.
abstract: We report the solution three-dimensional structure of an alphaA-conotoxin EIVA determined by nuclear magnetic resonance spectroscopy and restrained molecular dynamics. The alphaA-conotoxin EIVA consists of 30 amino acids representing the largest peptide among the alpha/alphaA-family conotoxins discovered so far and targets the neuromuscular nicotinic acetylcholine receptor with high affinity. alphaA-Conotoxin EIVA consists of three distinct structural domains. The first domain is mainly composed of the Cys3-Cys11-disulfide loop and is structurally ill-defined with a large backbone root mean square deviation of 1.91 A. The second domain formed by residues His12-Hyp21 is extremely well defined with a backbone root mean square deviation of 0.52 A, thus forming a sturdy stem for the entire molecule. The third C-terminal domain formed by residues Hyp22-Gly29 shows an intermediate structural order having a backbone root mean square deviation of 1.04 A. A structurally ill-defined N-terminal first loop domain connected to a rigid central molecular stem seems to be the general structural feature of the alphaA-conotoxin subfamily. A detailed structural comparison between alphaA-conotoxin EIVA and alphaA-conotoxin PIVA suggests that the higher receptor affinity of alphaA-conotoxin EIVA than alphaA-conotoxin PIVA might originate from different steric disposition and charge distribution in the second loop "handle" motif.
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: Seung-Wook
authors.initials: SW
authors.lastname: Chi
authors.forename: Kyu-Hwan
authors.initials: KH
authors.lastname: Park
authors.forename: Jae-Eun
authors.initials: JE
authors.lastname: Suk
authors.forename: Baldomero M
authors.initials: BM
authors.lastname: Olivera
authors.forename: J Michael
authors.initials: JM
authors.lastname: McIntosh
authors.forename: Kyou-Hoon
authors.initials: KH
authors.lastname: Han
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020916:Conotoxins / Q000737:chemistry*; D008958:Models, Molecular; D008978:Mollusk Venoms / Q000737:chemistry*; D018733:Nicotinic Antagonists / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D012996:Solutions; D040681:Structural Homology, Protein
chemical_list: D020916:Conotoxins; D008978:Mollusk Venoms; D018733:Nicotinic Antagonists; D012996:Solutions; C108141:conotoxin EIVA