Nuclear magnetic resonance solution conformation of alpha-conotoxin AuIB, an alpha(3)beta(4) subtype-selective neuronal nicotinic acetylcholine receptor antagonist.
The neuronal nicotinic acetylcholine receptors constitute a highly diverse group, with subtypes consisting of pentameric combinations of alpha and beta subunits. alpha-Conotoxins are a homologous series of small peptides that antagonize these receptors. We present the three-dimensional solution structure of alpha-conotoxin AuIB, the first 15-residue alpha-conotoxin known to selectively block the alpha(3)beta(4) nicotinic acetylcholine receptor subtype. The pairwise backbone and heavy-atom root mean square deviation for an ensemble of 20 structures are 0.269 and 0.720 A, respectively. The overall fold of alpha-conotoxin AuIB closely resembles that of the alpha4/7 subfamily alpha-conotoxins. However, the absence of Tyr(15), normally present in other alpha4/7 members, results in tight bending of the backbone at the C terminus and effectively renders Asp(14) to assume the spatial location of Tyr(15) present in other neuronal alpha4/7 alpha-conotoxins. Structural comparison of alpha-conotoxin AuIB with the alpha(3)beta(2) subtype-specific alpha-conotoxin MII shows different electrostatic surface charge distributions, which may be important in differential receptor subtype recognition.
Cho
J H
JH
Protein Engineering Laboratory, Korea Research Institute of Bioscience and Biotechnology, Yusong, Taejon 305-600, Republic of Korea.
Mok
K H
KH
Olivera
B M
BM
McIntosh
J M
JM
Park
K H
KH
Han
K H
KH
D000595:Amino Acid Sequence; D020916:Conotoxins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects; D018733:Nicotinic Antagonists / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011978:Receptors, Nicotinic; D012996:Solutions; D055672:Static Electricity; D013499:Surface Properties
D020916:Conotoxins; D009419:Nerve Tissue Proteins; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D012996:Solutions; C115558:conotoxin AuIB; C403530:nicotinic receptor alpha3beta4