دورية أكاديمية
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 |
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| المؤلفون: | Teixeira-Duarte, CM, Fonseca, F, Morais-Cabral, JH |
| المساهمون: | Instituto de Investigação e Inovação em Saúde |
| بيانات النشر: | eLife Sciences Publications |
| سنة النشر: | 2019 |
| المجموعة: | Repositório Aberto da Universidade do Porto |
| مصطلحات موضوعية: | Adenosine Triphosphate / chemistry, Bacillus subtilis / chemistry, Bacillus subtilis / genetics, Bacterial Proteins / chemistry, Bacterial Proteins / genetics, Bacterial Proteins / ultrastructure, Binding Sites / genetics, Calcium / metabolism, Cation Transport Proteins / chemistry, Cation Transport Proteins / genetics, Cation Transport Proteins / ultrastructure, Cations / chemistry, Crystallography, X-Ray, Kv1.6 Potassium Channel / chemistry, Kv1.6 Potassium Channel / ultrastructure, Nucleotides / chemistry, Nucleotides / genetics, Potassium / chemistry, Potassium / metabolism, Potassium Channels / chemistry, Potassium Channels / genetics, Potassium Channels / ultrastructure, Protein Conformation, Protein Domains / genetics, Protein Structure, Tertiary, Ribosomal Proteins |
| 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2050-084X |
| العلاقة: | eLife, vol.8:e50661; https://elifesciences.org/articles/50661Test; https://hdl.handle.net/10216/138997Test |
| DOI: | 10.7554/eLife.50661 |
| الإتاحة: | https://doi.org/10.7554/eLife.50661Test https://hdl.handle.net/10216/138997Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.25BE17D5 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.50661 |