Activation of a nucleotide-dependent RCK domain requires binding of a cation cofactor to a conserved site
| Autor: | Celso M. Teixeira-Duarte, J.H. Morais Cabral, Fátima Fonseca |
|---|---|
| Přispěvatelé: | Instituto de Investigação e Inovação em Saúde |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Potassium Channels
KtrAB Protein Conformation Dimer Structural Biology and Molecular Biophysics Potassium / chemistry Crystallography X-Ray chemistry.chemical_compound Adenosine Triphosphate Potassium Channels / genetics Bacillus subtilis / genetics B. subtilis Adenosine Triphosphate / chemistry Nucleotide Bacillus subtilis / chemistry Biology (General) Cation Transport Proteins chemistry.chemical_classification biology Chemistry Nucleotides General Neuroscience General Medicine Bacterial Proteins / chemistry RCK domain Transport protein Kv1.6 Potassium Channel / ultrastructure Cation Transport Proteins / ultrastructure Potassium Channels / chemistry Medicine Nucleotides / genetics molecular mechanism Research Article Bacillus subtilis Ribosomal Proteins Bacterial Proteins / ultrastructure Cation Transport Proteins / genetics Bacterial Proteins / genetics Calcium / metabolism QH301-705.5 Science Potassium / metabolism Protein Domains / genetics General Biochemistry Genetics and Molecular Biology Cofactor Divalent Bacterial Proteins Protein Domains Cations Potassium Channels / ultrastructure Binding site Cation Transport Proteins / chemistry Binding Sites General Immunology and Microbiology Nucleotides / chemistry Transporter Kv1.6 Potassium Channel Binding Sites / genetics Protein Structure Tertiary Kv1.6 Potassium Channel / chemistry Cations / chemistry Structural biology biology.protein Biophysics Potassium Calcium |
| Zdroj: | eLife 'eLife ', vol: 8, pages: e50661-1-e50661-28 (2019) eLife, Vol 8 (2019) |
| ISSN: | 2050-084X |
| Popis: | 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 ¿-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. We thank access to ALBA (XALOC), ESRF (ID23-1) and Soleil (PROXIMA 1 and 2a) synchrotrons and technical support provided by the i3S scientific platform ‘Biochemical and Biophysical Technologies’ and FCUP|DQB-Lab and Services. Work was supported by Fundação Luso-Americana para o Desenvolvimento through the FLAD Life Science 2020 award entitled ‘Bacterial K+ transporters are potential antimicrobial targets: mechanisms of transport and regulation’ and by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the projects POCI-01–0145-FEDER-029863 (PTDC/BIA-BQM/29863/2017) and ‘Institute for Research and Innovation in Health Sciences’ (POCI-01–0145-FEDER-007274).’ CMT-D was supported by FCT fellowship (SFRH/BD/123761/2016) and FF was supported by FCT fellowship (SFRH/BPD/102753/2014). |
| Databáze: | OpenAIRE |
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