Canle iónica regulada por voltaxe: Diferenzas entre revisións

 

A principal parte funcional do dominio proteico sensible á voltaxe destas canles contén xeralmente unha rexión composta das hélices S3b e S4, coñecida como a "pa" ("''paddle''") debido á súa forma, que parece ser unha [[secuencia conservada]], intercambiable a través dunha gran variedade de células e especies. Unha "pa" sensora de voltaxe similar encontrouse tamén na familia das [[fosfatase sensible á voltaxe|fosfatases sensibles á voltaxe]] en varias especies.<ref>{{cite journal | vauthors = Murata Y, Iwasaki H, Sasaki M, Inaba K, Okamura Y | title = Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor | journal = Nature | volume = 435 | issue = 7046 | pages = 1239–43 | date = June 2005 | pmid = 15902207 | pmc = | doi = 10.1038/nature03650 | bibcode = 2005Natur.435.1239M }}</ref> A substitución por [[enxeñaría xenética]] da rexión da pa dunha especie de [[arquea]] que habita en zonas volcánicas a canles de potasio de cerebro de rata ten como resultado unha canle iónica completamente funcional, con tal de que se substitúa a "pa" intacta completa.<ref name="pmid18004375">{{cite journal | vauthors = Alabi AA, Bahamonde MI, Jung HJ, Kim JI, Swartz KJ | title = Portability of paddle motif function and pharmacology in voltage sensors | journal = Nature | volume = 450 | issue = 7168 | pages = 370–5 | date = November 2007 | pmid = 18004375 | pmc = 2709416 | doi = 10.1038/nature06266 | bibcode = 2007Natur.450..370A }}</ref> Esta "modularidade" permite o uso de sistemas modelo simples e baratos para estudar a función desta rexión, o seu papel en enfermidades, e o control farmacéutico do seu comportamento en vez de estar limitado a preparacións difíciles de estudar e pouco caracterizadas.<ref name="pmid18004376">{{cite journal | vauthors = Long SB, Tao X, Campbell EB, MacKinnon R | title = Atomic structure of a voltage-dependent K⁺ channel in a lipid membrane-like environment | journal = Nature | volume = 450 | issue = 7168 | pages = 376–82 | date = November 2007 | pmid = 18004376 | doi = 10.1038/nature06265 | bibcode = 2007Natur.450..376L }}</ref>

 

The gate is thought to be coupled to the voltage sensing regions of the channels and appears to contain a mechanical obstruction to ion flow.<ref>{{cite journal | vauthors = Yellen G | title = The moving parts of voltage-gated ion channels | journal = Quarterly Reviews of Biophysics | volume = 31 | issue = 3 | pages = 239–95 | date = August 1998 | pmid = 10384687 | doi=10.1017/s0033583598003448}}</ref> While the S6 domain has been agreed upon as the segment acting as this obstruction, its exact mechanism is unknown. Possible explanations include: the S6 segment makes a scissor-like movement allowing ions to flow through,<ref>{{cite journal | vauthors = Perozo E, Cortes DM, Cuello LG | title = Structural rearrangements underlying K⁺-channel activation gating | journal = Science | volume = 285 | issue = 5424 | pages = 73–8 | date = July 1999 | pmid = 10390363 | doi=10.1126/science.285.5424.73}}</ref> the S6 segment breaks into two segments allowing of passing of ions through the channel,<ref name="Jiang_2002">{{cite journal | vauthors = Jiang Y, Lee A, Chen J, Cadene M, Chait BT, MacKinnon R | title = Crystal structure and mechanism of a calcium-gated potassium channel | journal = Nature | volume = 417 | issue = 6888 | pages = 515–22 | date = May 2002 | pmid = 12037559 | doi = 10.1038/417515a | bibcode = 2002Natur.417..515J }}</ref> or the S6 channel serving as the gate itself.<ref>{{cite journal | vauthors = Webster SM, Del Camino D, Dekker JP, Yellen G | title = Intracellular gate opening in Shaker K⁺ channels defined by high-affinity metal bridges | journal = Nature | volume = 428 | issue = 6985 | pages = 864–8 | date = April 2004 | pmid = 15103379 | doi = 10.1038/nature02468 | bibcode = 2004Natur.428..864W }}</ref> The mechanism by which the movement of the S4 segment affects that of S6 is still unknown, however it is theorized that there is a S4-S5 linker whose movement allows the opening of S6.<ref name="Bezanilla_2005" />