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Rational design of new NO and redox sensitivity into connexin26 hemichannels
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Meigh, Louise, Cook, Daniel Sean, Zhang, Jie and Dale, Nicholas (2015) Rational design of new NO and redox sensitivity into connexin26 hemichannels. Open Biology, Volume 5 (Number 2). pp. 1-9. Article number 140208. doi:10.1098/rsob.140208 ISSN 2046-2441.
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Official URL: http://dx.doi.org/10.1098/rsob.140208
Abstract
CO2 directly opens hemichannels of connexin26 (Cx26) by carbamylating K125, thereby allowing salt bridge formation with R104 of the neighbouring subunit in the connexin hexamer. The formation of the inter-subunit carbamate bridges within the hexameric hemichannel traps it in the open state. Here, we use insights derived from this model to test whether the range of agonists capable of opening Cx26 can be extended by promoting the formation of analogous inter-subunit bridges via different mechanisms. The mutation K125C gives potential for nitrosylation on Cys125 and formation of an SNO bridge to R104 of the neighbouring subunit. Unlike wild-type Cx26 hemichannels, which are insensitive to NO and NO2−, hemichannels comprising Cx26K125C can be opened by NO2− and NO donors. However, NO2− was unable to modulate the doubly mutated (K125C, R104A) hemichannels, indicating that an inter-subunit bridge between C125 and R104 is required for the opening action of NO2−. In a further test, we introduced two mutations into Cx26, K125C and R104C, to allow disulfide bridge formation across the inter-subunit boundary. These doubly mutated hemichannels open in response to changes in intracellular redox potential.
Item Type: | Journal Article | ||||||||
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Subjects: | Q Science > QH Natural history > QH301 Biology | ||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||
Library of Congress Subject Headings (LCSH): | Gap junctions (Cell biology), Oxidation-reduction reaction | ||||||||
Journal or Publication Title: | Open Biology | ||||||||
Publisher: | The Royal Society Publishing | ||||||||
ISSN: | 2046-2441 | ||||||||
Official Date: | February 2015 | ||||||||
Dates: |
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Volume: | Volume 5 | ||||||||
Number: | Number 2 | ||||||||
Number of Pages: | 9 | ||||||||
Page Range: | pp. 1-9 | ||||||||
Article Number: | Article number 140208 | ||||||||
DOI: | 10.1098/rsob.140208 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||
Description: | Dataset can be found on publishers website. |
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Date of first compliant deposit: | 29 December 2015 | ||||||||
Date of first compliant Open Access: | 29 December 2015 |
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