scholarly journals Molecular Determinants and Role of An Anion Binding Site in the External Mouth of the CFTR Chloride Channel Pore

2003 ◽  
Vol 549 (2) ◽  
pp. 387-397 ◽  
Author(s):  
Xiandi Gong ◽  
Paul Linsdell
Keyword(s):  
Binding Site ◽  
Chloride Channel ◽  
Anion Binding ◽  
Channel Pore ◽  
Molecular Determinants

Thiocyanate as a probe of the cystic fibrosis transmembrane conductance regulator chloride channel pore

2001 ◽  
Vol 79 (7) ◽  
pp. 573-579 ◽  
Author(s):  
Paul Linsdell
Keyword(s):  
Cystic Fibrosis ◽  
Steady State ◽  
Mole Fraction ◽  
Chloride Channel ◽  
Theory Model ◽  
Anion Binding ◽  
Rate Theory ◽  
Patch Clamp Recording ◽  
Channel Pore ◽  
Mammalian Cell Lines

Immediately following exposure to thiocyanate (SCN–)-containing solutions, the cystic fibrosis conductance regulator Cl– channel exhibits high unitary SCN– conductance and anomalous mole fraction behaviour, suggesting the presence of multiple anion binding sites within the channel pore. However, under steady-state conditions SCN– conductance is very low. Here I show, using patch clamp recording from CFTR-transfected mammalian cell lines, that under steady-state conditions neither SCN– conductance nor SCN– permeability show anomalous mole fraction behaviour. Instead, SCN– conductance, permeability, and block of Cl– permeation can all be reproduced by a rate theory model that assumes only a single intrapore anion binding site. These results suggest that under steady-state conditions the interaction between SCN– and the CFTR channel pore can be understood by a simple model whereby SCN– ions enter the pore more easily than Cl–, and bind within the pore more tightly than Cl–. The implications of these findings for investigating and understanding the mechanism of anion permeation are discussed.Key words: chloride channel, permeation, anion binding, multi-ion pore behaviour, rate theory model.

scholarly journals Role of the Anion-Binding Site in Catalysis and Regulation ofMycobacterium tuberculosisd-3-Phosphoglycerate Dehydrogenase

Biochemistry ◽  
2009 ◽  
Vol 48 (22) ◽  
pp. 4808-4815 ◽  
Author(s):  
Rodney L. Burton ◽  
Shawei Chen ◽  
Xiao Lan Xu ◽  
Gregory A. Grant
Keyword(s):  
Binding Site ◽  
Anion Binding ◽  
Phosphoglycerate Dehydrogenase

scholarly journals Permeation and Block of the Skeletal Muscle Chloride Channel, ClC-1, by Foreign Anions

1998 ◽  
Vol 111 (5) ◽  
pp. 653-665 ◽  
Author(s):  
G.Y. Rychkov ◽  
M. Pusch ◽  
M.L. Roberts ◽  
T.J. Jentsch ◽  
A.H. Bretag
Keyword(s):  
Skeletal Muscle ◽  
Binding Site ◽  
Chloride Channel ◽  
Chloride Channels ◽  
Single Channel ◽  
Hydrophobic Interactions ◽  
Channel Pore ◽  
Channel Opening ◽  
Voltage Dependent ◽  
Significant Block

A distinctive feature of the voltage-dependent chloride channels ClC-0 (the Torpedo electroplaque chloride channel) and ClC-1 (the major skeletal muscle chloride channel) is that chloride acts as a ligand to its own channel, regulating channel opening and so controlling the permeation of its own species. We have now studied the permeation of a number of foreign anions through ClC-1 using voltage-clamp techniques on Xenopus oocytes and Sf9 cells expressing human (hClC-1) or rat (rClC-1) isoforms, respectively. From their effect on channel gating, the anions presented in this paper can be divided into three groups: impermeant or poorly permeant anions that can not replace Cl− as a channel opener and do not block the channel appreciably (glutamate, gluconate, HCO3−, BrO3−); impermeant anions that can open the channel and show significant block (methanesulfonate, cyclamate); and permeant anions that replace Cl− at the regulatory binding site but impair Cl− passage through the channel pore (Br−, NO3−, ClO3−, I−, ClO4−, SCN−). The permeability sequence for rClC-1, SCN− ∼ ClO4− > Cl− > Br− > NO3− ∼ ClO3− > I− >> BrO3− > HCO3− >> methanesulfonate ∼ cyclamate ∼ glutamate, was different from the sequence determined for blocking potency and ability to shift the Popen curve, SCN− ∼ ClO4− > I− > NO3− ∼ ClO3− ∼ methanesulfonate > Br− > cyclamate > BrO3− > HCO3− > glutamate, implying that the regulatory binding site that opens the channel is different from the selectivity center and situated closer to the external side. Channel block by foreign anions is voltage dependent and can be entirely accounted for by reduction in single channel conductance. Minimum pore diameter was estimated to be ∼4.5 Å. Anomalous mole-fraction effects found for permeability ratios and conductance in mixtures of Cl− and SCN− or ClO4− suggest a multi-ion pore. Hydrophobic interactions with the wall of the channel pore may explain discrepancies between the measured permeabilities of some anions and their size.

Dual Role of Lys206−Lys296 Interaction in Human Transferrin N-Lobe:  Iron-Release Trigger and Anion-Binding Site†

Biochemistry ◽  
1999 ◽  
Vol 38 (30) ◽  
pp. 9704-9711 ◽  
Author(s):  
Qing-Yu He ◽  
Anne B. Mason ◽  
Beatrice M. Tam ◽  
Ross T. A. MacGillivray ◽  
Robert C. Woodworth
Keyword(s):  
Binding Site ◽  
Dual Role ◽  
Anion Binding ◽  
Iron Release ◽  
Human Transferrin
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