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Binary architecture of the Nav1.2-β2 signaling complex

(2016) ELIFE. 5.
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Abstract
To investigate the mechanisms by which beta-subunits influence Nav channel function, we solved the crystal structure of the beta 2 extracellular domain at 1.35A. We combined these data with known bacterial Nav channel structural insights and novel functional studies to determine the interactions of specific residues in beta 2 with Nav1.2. We identified a flexible loop formed by (72)Cys and (75)Cys, a unique feature among the four beta-subunit isoforms. Moreover, we found that (55)Cys helps to determine the influence of beta 2 on Nav1.2 toxin susceptibility. Further mutagenesis combined with the use of spider toxins reveals that (55)Cys forms a disulfide bond with 91 Cys in the Nav1.2 domain II pore loop, thereby suggesting a 1:1 stoichiometry. Our results also provide clues as to which disulfide bonds are formed between adjacent Nav1.2 (CyS)-Cy-912/918 residues. The concepts emerging from this work will help to form a model reflecting the beta-subunit location in a Nav channel complex.
Keywords
GATED SODIUM-CHANNEL, DEPENDENT K+ CHANNEL, O-CONOTOXIN GVIIJ, BETA-SUBUNITS, CRYSTAL-STRUCTURE, CALCIUM-CHANNEL, ALPHA-SUBUNITS, ATRIAL-FIBRILLATION, AUXILIARY SUBUNIT, CARDIAC MYOCYTES

Citation

Please use this url to cite or link to this publication:

Chicago
Das, Samir, John Gilchrist, Frank Bosmans, and Filip Van Petegem. 2016. “Binary Architecture of the Nav1.2-β2 Signaling Complex.” Elife 5.
APA
Das, Samir, Gilchrist, J., Bosmans, F., & Van Petegem, F. (2016). Binary architecture of the Nav1.2-β2 signaling complex. ELIFE, 5.
Vancouver
1.
Das S, Gilchrist J, Bosmans F, Van Petegem F. Binary architecture of the Nav1.2-β2 signaling complex. ELIFE. 2016;5.
MLA
Das, Samir, John Gilchrist, Frank Bosmans, et al. “Binary Architecture of the Nav1.2-β2 Signaling Complex.” ELIFE 5 (2016): n. pag. Print.
@article{8584512,
  abstract     = {To investigate the mechanisms by which beta-subunits influence Nav channel function, we solved the crystal structure of the beta 2 extracellular domain at 1.35A. We combined these data with known bacterial Nav channel structural insights and novel functional studies to determine the interactions of specific residues in beta 2 with Nav1.2. We identified a flexible loop formed by (72)Cys and (75)Cys, a unique feature among the four beta-subunit isoforms. Moreover, we found that (55)Cys helps to determine the influence of beta 2 on Nav1.2 toxin susceptibility. Further mutagenesis combined with the use of spider toxins reveals that (55)Cys forms a disulfide bond with 91 Cys in the Nav1.2 domain II pore loop, thereby suggesting a 1:1 stoichiometry. Our results also provide clues as to which disulfide bonds are formed between adjacent Nav1.2 (CyS)-Cy-912/918 residues. The concepts emerging from this work will help to form a model reflecting the beta-subunit location in a Nav channel complex.},
  articleno    = {e10960},
  author       = {Das, Samir and Gilchrist, John and Bosmans, Frank and Van Petegem, Filip},
  issn         = {2050-084X},
  journal      = {ELIFE},
  language     = {eng},
  pages        = {21},
  title        = {Binary architecture of the Nav1.2-\ensuremath{\beta}2 signaling complex},
  url          = {http://dx.doi.org/10.7554/elife.10960},
  volume       = {5},
  year         = {2016},
}

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