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Nature
2007 Nov 15;4507168:370-5. doi: 10.1038/nature06266.
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Portability of paddle motif function and pharmacology in voltage sensors.
Alabi AA, Bahamonde MI, Jung HJ, Kim JI, Swartz KJ.
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Voltage-sensing domains enable membrane proteins to sense and react to changes in membrane voltage. Although identifiable S1-S4 voltage-sensing domains are found in an array of conventional ion channels and in other membrane proteins that lack pore domains, the extent to which their voltage-sensing mechanisms are conserved is unknown. Here we show that the voltage-sensor paddle, a motif composed of S3b and S4 helices, can drive channel opening with membrane depolarization when transplanted from an archaebacterial voltage-activated potassium channel (KvAP) or voltage-sensing domain proteins (Hv1 and Ci-VSP) into eukaryotic voltage-activated potassium channels. Tarantula toxins that partition into membranes can interact with these paddle motifs at the protein-lipid interface and similarly perturb voltage-sensor activation in both ion channels and proteins with a voltage-sensing domain. Our results show that paddle motifs are modular, that their functions are conserved in voltage sensors, and that they move in the relatively unconstrained environment of the lipid membrane. The widespread targeting of voltage-sensor paddles by toxins demonstrates that this modular structural motif is an important pharmacological target.
Aggarwal,
Contribution of the S4 segment to gating charge in the Shaker K+ channel.
1996, Pubmed,
Xenbase
Aggarwal,
Contribution of the S4 segment to gating charge in the Shaker K+ channel.
1996,
Pubmed
,
Xenbase Ahern,
Specificity of charge-carrying residues in the voltage sensor of potassium channels.
2004,
Pubmed Ahern,
Stirring up controversy with a voltage sensor paddle.
2004,
Pubmed Campos,
Two atomic constraints unambiguously position the S4 segment relative to S1 and S2 segments in the closed state of Shaker K channel.
2007,
Pubmed
,
Xenbase Chanda,
Gating charge displacement in voltage-gated ion channels involves limited transmembrane movement.
2005,
Pubmed Cuello,
Molecular architecture of the KvAP voltage-dependent K+ channel in a lipid bilayer.
2004,
Pubmed Frech,
A novel potassium channel with delayed rectifier properties isolated from rat brain by expression cloning.
1989,
Pubmed
,
Xenbase Garcia,
Purification and characterization of three inhibitors of voltage-dependent K+ channels from Leiurus quinquestriatus var. hebraeus venom.
1994,
Pubmed
,
Xenbase Grabe,
Structure prediction for the down state of a potassium channel voltage sensor.
2007,
Pubmed Herrington,
Blockers of the delayed-rectifier potassium current in pancreatic beta-cells enhance glucose-dependent insulin secretion.
2006,
Pubmed Hoshi,
Biophysical and molecular mechanisms of Shaker potassium channel inactivation.
1990,
Pubmed
,
Xenbase Jiang,
X-ray structure of a voltage-dependent K+ channel.
2003,
Pubmed Jiang,
The principle of gating charge movement in a voltage-dependent K+ channel.
2003,
Pubmed Jung,
Solution structure and lipid membrane partitioning of VSTx1, an inhibitor of the KvAP potassium channel.
2005,
Pubmed Kubo,
Primary structure and functional expression of a mouse inward rectifier potassium channel.
1993,
Pubmed
,
Xenbase Lampe,
Isolation and pharmacological characterization of omega-grammotoxin SIA, a novel peptide inhibitor of neuronal voltage-sensitive calcium channel responses.
1993,
Pubmed Lee,
Lipid-protein interactions in biological membranes: a structural perspective.
2003,
Pubmed Lee,
Structure of the KvAP voltage-dependent K+ channel and its dependence on the lipid membrane.
2005,
Pubmed Lee,
Solution structure and functional characterization of SGTx1, a modifier of Kv2.1 channel gating.
2004,
Pubmed
,
Xenbase Lee,
Interaction between extracellular Hanatoxin and the resting conformation of the voltage-sensor paddle in Kv channels.
2003,
Pubmed
,
Xenbase Lee,
A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom.
2004,
Pubmed Li-Smerin,
Localization and molecular determinants of the Hanatoxin receptors on the voltage-sensing domains of a K(+) channel.
2000,
Pubmed
,
Xenbase Li-Smerin,
Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels.
1998,
Pubmed
,
Xenbase Li-Smerin,
Helical structure of the COOH terminus of S3 and its contribution to the gating modifier toxin receptor in voltage-gated ion channels.
2001,
Pubmed Long,
Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment.
2007,
Pubmed Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed Long,
Voltage sensor of Kv1.2: structural basis of electromechanical coupling.
2005,
Pubmed Lu,
Coupling between voltage sensors and activation gate in voltage-gated K+ channels.
2002,
Pubmed
,
Xenbase Lu,
Ion conduction pore is conserved among potassium channels.
2001,
Pubmed Milescu,
Tarantula toxins interact with voltage sensors within lipid membranes.
2007,
Pubmed
,
Xenbase Murata,
Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor.
2005,
Pubmed
,
Xenbase Papazian,
Electrostatic interactions of S4 voltage sensor in Shaker K+ channel.
1995,
Pubmed
,
Xenbase Phillips,
Voltage-sensor activation with a tarantula toxin as cargo.
2005,
Pubmed Ramsey,
A voltage-gated proton-selective channel lacking the pore domain.
2006,
Pubmed Ruta,
Localization of the voltage-sensor toxin receptor on KvAP.
2004,
Pubmed Ruta,
Calibrated measurement of gating-charge arginine displacement in the KvAP voltage-dependent K+ channel.
2005,
Pubmed Ruta,
Functional analysis of an archaebacterial voltage-dependent K+ channel.
2003,
Pubmed Sasaki,
A voltage sensor-domain protein is a voltage-gated proton channel.
2006,
Pubmed Schmidt,
Phospholipids and the origin of cationic gating charges in voltage sensors.
2006,
Pubmed Seoh,
Voltage-sensing residues in the S2 and S4 segments of the Shaker K+ channel.
1996,
Pubmed
,
Xenbase Siemens,
Spider toxins activate the capsaicin receptor to produce inflammatory pain.
2006,
Pubmed Soler-Llavina,
Functional interactions at the interface between voltage-sensing and pore domains in the Shaker K(v) channel.
2006,
Pubmed
,
Xenbase Swartz,
Tarantula toxins interacting with voltage sensors in potassium channels.
2007,
Pubmed Swartz,
Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites.
1997,
Pubmed
,
Xenbase Swartz,
Mapping the receptor site for hanatoxin, a gating modifier of voltage-dependent K+ channels.
1997,
Pubmed Swartz,
Towards a structural view of gating in potassium channels.
2004,
Pubmed Swartz,
An inhibitor of the Kv2.1 potassium channel isolated from the venom of a Chilean tarantula.
1995,
Pubmed Tempel,
Sequence of a probable potassium channel component encoded at Shaker locus of Drosophila.
1987,
Pubmed Tombola,
The twisted ion-permeation pathway of a resting voltage-sensing domain.
2007,
Pubmed
,
Xenbase Tombola,
How far will you go to sense voltage?
2005,
Pubmed
