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Structural determinants of CO2-sensitivity in the β connexin family suggested by evolutionary analysis
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Dospinescu, Valentin-Mihai, Nijjar, Sarbjit, Spanos, Fokion, Cook, Jonathan P., de Wolf, Elizabeth, Biscotti, Maria Assunta, Gerdol, Marco and Dale, Nicholas (2019) Structural determinants of CO2-sensitivity in the β connexin family suggested by evolutionary analysis. Communications Biology, 2 (1). 331 . doi:10.1038/s42003-019-0576-2 ISSN 2399-3642.
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Official URL: http://dx.doi.org/10.1038/s42003-019-0576-2
Abstract
A subclade of connexins comprising Cx26, Cx30, and Cx32 are directly sensitive to CO2. CO2 binds to a carbamylation motif present in these connexins and causes their hemichannels to open. Cx26 may contribute to CO2-dependent regulation of breathing in mammals. Here, we show that the carbamylation motif occurs in a wide range of non-mammalian vertebrates and was likely present in the ancestor of all gnathostomes. While the carbamylation motif is essential for connexin CO2-sensitivity, it is not sufficient. In Cx26 of amphibia and lungfish, an extended C-terminal tail prevents CO2-evoked hemichannel opening despite the presence of the motif. Although Cx32 has a long C-terminal tail, Cx32 hemichannels open to CO2 because the tail is conformationally restricted by the presence of proline residues. The loss of the C-terminal tail of Cx26 in amniotes was an evolutionary innovation that created a connexin hemichannel with CO2-sensing properties suitable for the regulation of breathing.
Item Type: | Journal Article | |||||||||||||||
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Subjects: | Q Science > QH Natural history Q Science > QP Physiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||||||||
Library of Congress Subject Headings (LCSH): | Connexins, Gap junctions (Cell biology) , Respiration, Respiration -- Regulation | |||||||||||||||
Journal or Publication Title: | Communications Biology | |||||||||||||||
Publisher: | Nature Publishing Group | |||||||||||||||
ISSN: | 2399-3642 | |||||||||||||||
Official Date: | 4 September 2019 | |||||||||||||||
Dates: |
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Volume: | 2 | |||||||||||||||
Number: | 1 | |||||||||||||||
Article Number: | 331 | |||||||||||||||
DOI: | 10.1038/s42003-019-0576-2 | |||||||||||||||
Status: | Peer Reviewed | |||||||||||||||
Publication Status: | Published | |||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
Date of first compliant deposit: | 11 September 2019 | |||||||||||||||
Date of first compliant Open Access: | 11 September 2019 | |||||||||||||||
RIOXX Funder/Project Grant: |
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