On the convergent evolution of animal toxins. Conservation of a diad of functional residues in potassium channel-blocking toxins with unrelated structures.
BgK is a K+ channel-blocking toxin from the sea anemone Bunodosoma granulifera. It is a 37-residue protein that adopts a novel fold, as determined by NMR and modeling. An alanine-scanning-based analysis revealed the functional importance of five residues, which include a critical lysine and an aromatic residue separated by 6.6 +/- 1.0 A. The same diad is found in the three known homologous toxins from sea anemones. More strikingly, a similar functional diad is present in all K+ channel-blocking toxins from scorpions, although these toxins adopt a distinct scaffold. Moreover, the functional diads of potassium channel-blocking toxins from sea anemone and scorpions superimpose in the three-dimensional structures. Therefore, toxins that have unrelated structures but similar functions possess conserved key functional residues, organized in an identical topology, suggesting a convergent functional evolution for these small proteins.
Dauplais
M
M
Département d'Ingénierie et d'Etudes des Protéines, CEA, Saclay, 91191 Gif-sur-Yvette Cedex, France.
Lecoq
A
A
Song
J
J
Cotton
J
J
Jamin
N
N
Gilquin
B
B
Roumestand
C
C
Vita
C
C
de Medeiros
C L
CL
Rowan
E G
EG
Harvey
A L
AL
Ménez
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D005075:Biological Evolution; D003064:Cnidarian Venoms / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017124:Conserved Sequence; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D026902:Potassium Channel Blockers; D017433:Protein Structure, Secondary; D012615:Sea Anemones; D017386:Sequence Homology, Amino Acid
D003064:Cnidarian Venoms; D026902:Potassium Channel Blockers; C104455:toxin BgK