A Two-Holed Story: Structural Secrets About ClC Proteins Become Unraveled?

Babini, Elena; Pusch, Michael

doi:10.1152/physiol.00019.2004

Cited by 10 publications

(5 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The crystal structure of two bacterial ClC channels has been described (Dutzler et al, 2002). Each ClC subunit, with a complex topology of 17 intramembrane a-helices, contributes a single pore to a dimeric 'doublebarrelled' ClC channel that contains two independently-gated pores, confirming the predictions of previous functional and structural investigations (reviewed by Estévez and Jentsch, 2002;Babini and Pusch, 2004;Chen, 2005;Dutzler, 2006). As found for ClC-4 and ClC-5, the prokaryotic ClC homologue functions as an H þ /Cl À antiporter, rather than as an ion channel (Accardi and Miller, 2004).…”

Section: Chloridesupporting

confidence: 62%

Ion Channels

Alexander¹,

Mathie²,

Peters³

2008

British J Pharmacology

View full text Add to dashboard Cite

Section: Chloridesupporting

confidence: 62%

Ion Channels

Alexander¹,

Mathie²,

Peters³

2008

British J Pharmacology

View full text Add to dashboard Cite

“…Although multiple open conductance states in the TOM core complex have been reported previously (9,20,26,34) no detailed characterization has been available so far. Previous studies on mitochondrial outer membranes and TOM complex channels of S. cerevisiae and N. crassa have focused on transitions between three approximately equidistant conductance levels (8,9,11,26,30,34) suggesting a ''doublebarrel'' model similar to that proposed for the ClC-0 chloride channel (63,64). In our records we did not observe equal spacing of the conductance levels and the transitions between them (see Table 2, last column), except at high voltages, where states S1, S2, and S3 display nonlinear I/V characteristics.…”

Section: Conductance Levelsmentioning

confidence: 96%

Dynamics of the Preprotein Translocation Channel of the Outer Membrane of Mitochondria

Poynor

Eckert

Nußberger

2008

Biophysical Journal

View full text Add to dashboard Cite

The protein translocase of the outer mitochondrial membrane (TOM) serves as the main entry site for virtually all mitochondrial proteins. Like many other protein translocases it also has an ion channel activity that can be used to study the dynamical properties of this supramolecular complex. We have purified TOM core complex and Tom40, the main pore forming subunit, from mitochondria of the filamentous fungus Neurospora crassa and incorporated them into planar lipid bilayers. We then examined their single channel properties to provide a detailed description of the conformational dynamics of this channel in the absence of its protein substrate. For isolated TOM core complex we have found at least six conductance states. Transitions between these states were voltage-dependent with a bell-shaped open probability distribution and distinct kinetics depending on the polarity of the applied voltage. The states with the largest conductance followed an Ohmic I/V characteristic consistent with a large cylindrical pore with very little interaction with the permeating ions. For the lower conductance states, however, we have observed inverted S-shaped nonlinear current-voltage curves reminiscent to those of much narrower pores where the permeating ions have to surmount an electrostatic energy barrier. At low voltages (<+/-70 mV), purified Tom40 protein did not show any transitions between its conductance states. Prolonged exposure to higher voltages induced similar gating behavior to what we observed for TOM core complex. This effect was time-dependent and reversible, indicating that Tom40 forms not only the pore but also contains the "gating machinery" of the complex. However, for proper functioning, additional proteins (Tom22, Tom7, Tom6, and Tom5) are required that act as a modulator of the pore dynamics by significantly reducing the energy barrier between different conformational states.

show abstract

“…This center portion is the narrowest part of the pore, formed by residues Tyr-445 and Ser-107 [ 19 ] and stabilizes Cl − ions from the water shell, which prevents the passage of uncharged solutes through this gate. A critical glutamic acid residue was identified whose side chain seems to occupy a third Cl − ion binding site in the closed state and that moves away to allow Cl − binding [ 111 , 112 ]. ClC has double-barreled pores, the pathways of which are determined by mutation analysis [ 7 – 9 ].…”

Section: Structure and Permeation Of CL − Channelsmentioning

confidence: 99%

Diversity of Cl− Channels

Morita

Iwamoto

2005

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Abstract. Cl -channels are widely found anion pores that are regulated by a variety of signals and that play various roles. On the basis of molecular biologic findings, ligand-gated Cl -channels in synapses, cystic fibrosis transmembrane conductors (CFTRs) and ClC channel types have been established, followed by bestrophin and possibly by tweety, which encode Ca 2+ -activated Cl -channels. The ClC family has been shown to possess a variety of functions, including stabilization of membrane potential, excitation, cellvolume regulation, fluid transport, protein degradation in endosomal vesicles and possibly cell growth. The molecular structure of Cl -channel types varies from 1 to 12 transmembrane segments. By means of computerbased prediction, functional Cl -channels have been synthesized artificially, revealing that many possible ion pores are hidden in channel, transporter or unidentified hydrophobic membrane proteins. Thus, novel Cl --conducting pores may be occasionally discovered, and evidence from molecular biologic studies will clarify their physiologic and pathophysiologic roles.

show abstract

A Two-Holed Story: Structural Secrets About ClC Proteins Become Unraveled?

Cited by 10 publications

References 49 publications

Ion Channels

Ion Channels

Dynamics of the Preprotein Translocation Channel of the Outer Membrane of Mitochondria

Diversity of Cl− Channels

Contact Info

Product

Resources

About