Abstract
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.
Keywords:
B. subtilis; KtrAB; RCK domain; molecular biophysics; molecular mechanism; structural biology.
© 2019, Teixeira-Duarte et al.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / chemistry
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Bacillus subtilis / chemistry
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Bacillus subtilis / genetics
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Bacterial Proteins / chemistry*
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Bacterial Proteins / genetics
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Bacterial Proteins / ultrastructure
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Binding Sites / genetics
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Calcium / metabolism
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Cation Transport Proteins / chemistry*
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Cation Transport Proteins / genetics
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Cation Transport Proteins / ultrastructure
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Cations / chemistry
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Crystallography, X-Ray
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Kv1.6 Potassium Channel / chemistry
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Kv1.6 Potassium Channel / ultrastructure
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Nucleotides / chemistry*
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Nucleotides / genetics
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Potassium / chemistry
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Potassium / metabolism
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Potassium Channels / chemistry
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Potassium Channels / genetics
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Potassium Channels / ultrastructure
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Protein Conformation*
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Protein Domains / genetics
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Protein Structure, Tertiary
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Ribosomal Proteins
Substances
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Bacterial Proteins
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Cation Transport Proteins
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Cations
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KtrB protein, Bacteria
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Kv1.6 Potassium Channel
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Nucleotides
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Potassium Channels
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Ribosomal Proteins
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ribosomal protein BL16
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Adenosine Triphosphate
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Potassium
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Calcium
Associated data
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PDB/6S2J
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PDB/6S5B
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PDB/6S5D
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PDB/6S7R
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PDB/6S5N
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PDB/6S5O
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PDB/6S5E
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PDB/6S5G
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PDB/6S5C
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PDB/4J90