Adoption of beta structure by the inactivating "ball" peptide of the Shaker B potassium channel.
The conformation of the inactivating peptide of the Shaker B K+ channel (ShB peptide) and that of a noninactivating mutant (ShBL7E peptide) have been studied. Under all experimental conditions explored, the mutant peptide remains in a predominantly nonordered conformation. On the contrary, the inactivating ShB peptide has a great tendency to adopt a highly stable beta structure, particularly when challenged "in vitro" by anionic phospholipid vesicles. Because the putative peptide binding elements at the inner mouth of the channel comprise a ring of anionic residues and a hydrophobic pocket, we hypothesize that the conformational restrictions imposed on the ShB peptide by its interaction with the anionic lipid vesicles could partly imitate those imposed by the above ion channel elements. Thus, we propose that adoption of beta structure by the inactivating peptide may also occur during channel inactivation. Moreover, the difficulties encountered by the noninactivating ShBL7E peptide mutant to adopt beta structure and the observation that trypsin hydrolysis of the ShB peptide prevent both structure formation and channel inactivation lend further support to the hypothesis that adoption of beta structure by the inactivating peptide in a hydrophobic environment is important in determining channel blockade.
Fernandez-Ballester
G
G
Department of Neurochemistry, University of Alicante, Spain.
Gavilanes
F
F
Albar
J P
JP
Criado
M
M
Ferragut
J A
JA
Gonzalez-Ros
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D004330:Drosophila; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry; D017354:Point Mutation; D026902:Potassium Channel Blockers; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared
D047908:Intracellular Signaling Peptides and Proteins; D010455:Peptides; D010743:Phospholipids; D026902:Potassium Channel Blockers; C076103:Shaker B inactivating peptide