Activation of a nucleotide-dependent RCK domain requires binding of a cation cofactor to a conserved site
| العنوان: | Activation of a nucleotide-dependent RCK domain requires binding of a cation cofactor to a conserved site |
|---|---|
| المؤلفون: | Celso M. Teixeira-Duarte, J.H. Morais Cabral, Fátima Fonseca |
| المساهمون: | Instituto de Investigação e Inovação em Saúde |
| المصدر: | eLife 'eLife ', vol: 8, pages: e50661-1-e50661-28 (2019) eLife, Vol 8 (2019) |
| بيانات النشر: | eLife Sciences Publications, Ltd, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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). |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2050-084X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1924106a515f93f57d68463a95168673Test http://europepmc.org/articles/PMC6957272Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1924106a515f93f57d68463a95168673 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2050084X |
|---|