Reversal of charge selectivity in transmembrane protein pores by using noncovalent molecular adapters.
In this study, the charge selectivity of staphylococcal alpha-hemolysin (alphaHL), a bacterial pore-forming toxin, is manipulated by using cyclodextrins as noncovalent molecular adapters. Anion-selective versions of alphaHL, including the wild-type pore and various mutants, become more anion selective when beta-cyclodextrin (betaCD) is lodged within the channel lumen. By contrast, the negatively charged adapter, hepta-6-sulfato-beta-cyclodextrin (s(7)betaCD), produces cation selectivity. The cyclodextrin adapters have similar effects when placed in cation-selective mutant alphaHL pores. Most probably, hydrated Cl(-) ions partition into the central cavity of betaCD more readily than K(+) ions, whereas s(7)betaCD introduces a charged ring near the midpoint of the channel lumen and confers cation selectivity through electrostatic interactions. The molecular adapters generate permeability ratios (P(K+)/P(Cl-)) over a 200-fold range and should be useful in the de novo design of membrane channels both for basic studies of ion permeation and for applications in biotechnology.
Gu
L Q
LQ
Department of Medical Biochemistry and Genetics, Texas A&M University System Health Science Center, College Station, TX 77843-1114, USA.
Dalla Serra
M
M
Vincent
J B
JB
Vigh
G
G
Cheley
S
S
Braha
O
O
Bayley
H
H
D000838:Anions; D001427:Bacterial Toxins / Q000737:chemistry* / Q000235:genetics; D002412:Cations; D003505:Cyclodextrins / Q000737:chemistry*; D005098:Exotoxins / Q000737:chemistry* / Q000235:genetics; D006460:Hemolysin Proteins / Q000737:chemistry* / Q000235:genetics; D016296:Mutagenesis
D000838:Anions; D001427:Bacterial Toxins; D002412:Cations; D003505:Cyclodextrins; D005098:Exotoxins; D006460:Hemolysin Proteins; C021091:staphylococcal alpha-toxin