Activation of a nucleotide-dependent RCK domain requires binding of a cation cofactor to a conserved site
RCK domains regulate the activity of K+ channels and transporters in eukaryotic and prokaryotic organisms by responding to ions or nucleotides. The mechanisms of RCK activation by Ca2+ in the eukaryotic BK and bacterial MthK K+ channels are well understood. However, the molecular details of activati...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-12-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/50661 |
| _version_ | 1811180999229308928 |
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| author | Celso M Teixeira-Duarte Fátima Fonseca João H Morais-Cabral |
| author_facet | Celso M Teixeira-Duarte Fátima Fonseca João H Morais-Cabral |
| author_sort | Celso M Teixeira-Duarte |
| collection | DOAJ |
| description | RCK domains regulate the activity of K+ channels and transporters in eukaryotic and prokaryotic organisms by responding to ions or nucleotides. The mechanisms of RCK activation by Ca2+ in the eukaryotic BK and bacterial MthK K+ channels are well understood. However, the molecular details of activation in nucleotide-dependent RCK domains are not clear. Through a functional and structural analysis of the mechanism of ATP activation in KtrA, a RCK domain from the B. subtilis KtrAB cation channel, we have found that activation by nucleotide requires binding of cations to an intra-dimer interface site in the RCK dimer. In particular, divalent cations are coordinated by the γ-phosphates of bound-ATP, tethering the two subunits and stabilizing the active state conformation. Strikingly, the binding site residues are highly conserved in many different nucleotide-dependent RCK domains, indicating that divalent cations are a general cofactor in the regulatory mechanism of many nucleotide-dependent RCK domains. |
| first_indexed | 2024-04-11T09:12:11Z |
| format | Article |
| id | doaj.art-e743e45d4994457e9a93601f3456d0e5 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:12:11Z |
| publishDate | 2019-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e743e45d4994457e9a93601f3456d0e52022-12-22T04:32:29ZengeLife Sciences Publications LtdeLife2050-084X2019-12-01810.7554/eLife.50661Activation of a nucleotide-dependent RCK domain requires binding of a cation cofactor to a conserved siteCelso M Teixeira-Duarte0https://orcid.org/0000-0002-8036-7069Fátima Fonseca1https://orcid.org/0000-0001-7979-5907João H Morais-Cabral2https://orcid.org/0000-0002-4461-9716Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal; Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, Portugal; Programa Doutoral em Biologia Molecular e Celular (MCbiology), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal; Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal; Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, PortugalRCK domains regulate the activity of K+ channels and transporters in eukaryotic and prokaryotic organisms by responding to ions or nucleotides. The mechanisms of RCK activation by Ca2+ in the eukaryotic BK and bacterial MthK K+ channels are well understood. However, the molecular details of activation in nucleotide-dependent RCK domains are not clear. Through a functional and structural analysis of the mechanism of ATP activation in KtrA, a RCK domain from the B. subtilis KtrAB cation channel, we have found that activation by nucleotide requires binding of cations to an intra-dimer interface site in the RCK dimer. In particular, divalent cations are coordinated by the γ-phosphates of bound-ATP, tethering the two subunits and stabilizing the active state conformation. Strikingly, the binding site residues are highly conserved in many different nucleotide-dependent RCK domains, indicating that divalent cations are a general cofactor in the regulatory mechanism of many nucleotide-dependent RCK domains.https://elifesciences.org/articles/50661RCK domainKtrABmolecular mechanism |
| spellingShingle | Celso M Teixeira-Duarte Fátima Fonseca João H Morais-Cabral Activation of a nucleotide-dependent RCK domain requires binding of a cation cofactor to a conserved site eLife RCK domain KtrAB molecular mechanism |
| title | Activation of a nucleotide-dependent RCK domain requires binding of a cation cofactor to a conserved site |
| title_full | Activation of a nucleotide-dependent RCK domain requires binding of a cation cofactor to a conserved site |
| title_fullStr | Activation of a nucleotide-dependent RCK domain requires binding of a cation cofactor to a conserved site |
| title_full_unstemmed | Activation of a nucleotide-dependent RCK domain requires binding of a cation cofactor to a conserved site |
| title_short | Activation of a nucleotide-dependent RCK domain requires binding of a cation cofactor to a conserved site |
| title_sort | activation of a nucleotide dependent rck domain requires binding of a cation cofactor to a conserved site |
| topic | RCK domain KtrAB molecular mechanism |
| url | https://elifesciences.org/articles/50661 |
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