Potassium channel selectivity filter dynamics revealed by single-molecule FRET. 2019

Shizhen Wang, and Sun-Joo Lee, and Grigory Maksaev, and Xin Fang, and Chong Zuo, and Colin G Nichols
Center for Investigation of Membrane Excitability Diseases, Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA. wangshizhen@umkc.edu.

Potassium (K) channels exhibit exquisite selectivity for conduction of K+ ions over other cations, particularly Na+. High-resolution structures reveal an archetypal selectivity filter (SF) conformation in which dehydrated K+ ions, but not Na+ ions, are perfectly coordinated. Using single-molecule FRET (smFRET), we show that the SF-forming loop (SF-loop) in KirBac1.1 transitions between constrained and dilated conformations as a function of ion concentration. The constrained conformation, essential for selective K+ permeability, is stabilized by K+ but not Na+ ions. Mutations that render channels nonselective result in dilated and dynamically unstable conformations, independent of the permeant ion. Further, while wild-type KirBac1.1 channels are K+ selective in physiological conditions, Na+ permeates in the absence of K+. Moreover, whereas K+ gradients preferentially support 86Rb+ fluxes, Na+ gradients preferentially support 22Na+ fluxes. This suggests differential ion selectivity in constrained versus dilated states, potentially providing a structural basis for this anomalous mole fraction effect.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D011188 Potassium An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D002463 Cell Membrane Permeability A quality of cell membranes which permits the passage of solvents and solutes into and out of cells. Permeability, Cell Membrane
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072760 Single Molecule Imaging High resolution imaging techniques that allow visualization of individual molecules of proteins, lipids, or nucleic acids within cells or tissues. Single Molecule Analysis,Single Molecule Tracking,Single Particle Analysis,Single Particle Imaging,Single Particle Microscopy,Single Particle Spectroscopy,Single Particle Tracking,Single Molecule Microscopy,Single Molecule Spectroscopy,Analyses, Single Particle,Analysis, Single Molecule,Analysis, Single Particle,Imaging, Single Molecule,Imaging, Single Particle,Microscopies, Single Particle,Microscopy, Single Molecule,Microscopy, Single Particle,Particle Tracking, Single,Single Molecule Analyses,Single Particle Analyses,Single Particle Microscopies,Single Particle Spectroscopies,Single Particle Trackings,Spectroscopy, Single Molecule,Spectroscopy, Single Particle,Tracking, Single Molecule,Tracking, Single Particle
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D012964 Sodium A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. Sodium Ion Level,Sodium-23,Ion Level, Sodium,Level, Sodium Ion,Sodium 23
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships

Related Publications

Shizhen Wang, and Sun-Joo Lee, and Grigory Maksaev, and Xin Fang, and Chong Zuo, and Colin G Nichols
January 2016, Nature structural & molecular biology,
Shizhen Wang, and Sun-Joo Lee, and Grigory Maksaev, and Xin Fang, and Chong Zuo, and Colin G Nichols
September 2017, Biochemical and biophysical research communications,
Shizhen Wang, and Sun-Joo Lee, and Grigory Maksaev, and Xin Fang, and Chong Zuo, and Colin G Nichols
January 2018, Methods in molecular biology (Clifton, N.J.),
Shizhen Wang, and Sun-Joo Lee, and Grigory Maksaev, and Xin Fang, and Chong Zuo, and Colin G Nichols
May 2017, Nature communications,
Shizhen Wang, and Sun-Joo Lee, and Grigory Maksaev, and Xin Fang, and Chong Zuo, and Colin G Nichols
November 2017, Nature,
Shizhen Wang, and Sun-Joo Lee, and Grigory Maksaev, and Xin Fang, and Chong Zuo, and Colin G Nichols
April 2020, Chemistry (Weinheim an der Bergstrasse, Germany),
Shizhen Wang, and Sun-Joo Lee, and Grigory Maksaev, and Xin Fang, and Chong Zuo, and Colin G Nichols
September 2008, Current protocols in nucleic acid chemistry,
Shizhen Wang, and Sun-Joo Lee, and Grigory Maksaev, and Xin Fang, and Chong Zuo, and Colin G Nichols
January 2018, Cell reports,
Shizhen Wang, and Sun-Joo Lee, and Grigory Maksaev, and Xin Fang, and Chong Zuo, and Colin G Nichols
April 2023, Communications biology,
Shizhen Wang, and Sun-Joo Lee, and Grigory Maksaev, and Xin Fang, and Chong Zuo, and Colin G Nichols
January 2013, Methods in cell biology,
Copied contents to your clipboard!