scholarly journals Distinct classes of potassium channels fused to GPCRs as electrical signaling biosensors

2021 ◽  
pp. 100119
Author(s):  
M. Dolores García-Fernández ◽  
Franck C. Chatelain ◽  
Hugues Nury ◽  
Anna Moroni ◽  
Christophe J. Moreau
eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
John D Lueck ◽  
Adam L Mackey ◽  
Daniel T Infield ◽  
Jason D Galpin ◽  
Jing Li ◽  
...  

C-type inactivation of potassium channels fine-tunes the electrical signaling in excitable cells through an internal timing mechanism that is mediated by a hydrogen bond network in the channels' selectively filter. Previously, we used nonsense suppression to highlight the role of the conserved Trp434-Asp447 indole hydrogen bond in Shaker potassium channels with a non-hydrogen bonding homologue of tryptophan, Ind (<xref ref-type="bibr" rid="bib36">Pless et al., 2013</xref>). Here, molecular dynamics simulations indicate that the Trp434Ind hydrogen bonding partner, Asp447, unexpectedly 'flips out' towards the extracellular environment, allowing water to penetrate the space behind the selectivity filter while simultaneously reducing the local negative electrostatic charge. Additionally, a protein engineering approach is presented whereby split intein sequences are flanked by endoplasmic reticulum retention/retrieval motifs (ERret) are incorporated into the N- or C- termini of Shaker monomers or within sodium channels two-domain fragments. This system enabled stoichiometric control of Shaker monomers and the encoding of multiple amino acids within a channel tetramer.


2019 ◽  
Vol 400 (10) ◽  
pp. 1303-1322 ◽  
Author(s):  
Marina Schrecker ◽  
Dorith Wunnicke ◽  
Inga Hänelt

Abstract Potassium channels play a crucial role in the physiology of all living organisms. They maintain the membrane potential and are involved in electrical signaling, pH homeostasis, cell-cell communication and survival under osmotic stress. Many prokaryotic potassium channels and members of the eukaryotic Slo channels are regulated by tethered cytoplasmic domains or associated soluble proteins, which belong to the family of regulator of potassium conductance (RCK). RCK domains and subunits form octameric rings, which control ion gating. For years, a common regulatory mechanism was suggested: ligand-induced conformational changes in the octameric ring would pull open a gate in the pore via flexible linkers. Consistently, ligand-dependent conformational changes were described for various RCK gating rings. Yet, recent structural and functional data of complete ion channels uncovered that the following signal transduction to the pore domains is divers. The different RCK-regulated ion channels show remarkably heterogeneous mechanisms with neither the connection from the RCK domain to the pore nor the gate being conserved. Some channels even lack the flexible linkers, while in others the gate cannot easily be assigned. In this review we compare available structures of RCK-gated potassium channels, highlight the similarities and differences of channel gating, and delineate existing inconsistencies.


2006 ◽  
Vol 33 (S 1) ◽  
Author(s):  
H. Fuellgraf ◽  
M. Steinkamp ◽  
M. Kolbe ◽  
A. Moser

2016 ◽  
Vol 12 (4) ◽  
pp. 36-44
Author(s):  
R.B. Strutynskyi ◽  
◽  
N.A. Strutynska ◽  
O.P. Maximyuk ◽  
M.O. Platonov ◽  
...  

Author(s):  
Igor S. Magura ◽  
Olena I. Magura ◽  
Olga V. Dolga ◽  
N. Kh. Pogorela ◽  
N. A. Bogdanova ◽  
...  

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