Dissecting the Molecular Mechanism of Nucleotide-Dependent Activation of the KtrAB K+ Transporter
| Autor: | Celso M. Teixeira-Duarte, Ricardo S. Vieira-Pires, João H. Morais-Cabral, Rita Gomes Rocha, Andras Szollosi |
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| Přispěvatelé: | Instituto de Investigação e Inovação em Saúde |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Potassium Channels Protein Conformation Physiology Cell Membranes Biochemistry Ion Channels chemistry.chemical_compound Protein structure Adenosine Triphosphate Structural mechanism C-di-amp Membrane region m-2c2 Medicine and Health Sciences Macromolecular Structure Analysis Membrane Technology Biology (General) Amino Acids Cation Transport Proteins Genetics Crystallography Organic Compounds General Neuroscience Physics Molecular Replacement Condensed Matter Physics Built Structures Transport protein Electrophysiology Chemistry Physical Sciences Crystal Structure Crystallographic Techniques Vibrio-alginolyticus Engineering and Technology Cellular Structures and Organelles General Agricultural and Biological Sciences Bacillus subtilis Research Article Protein Structure Gating ring Structural Engineering QH301-705.5 Structural similarity Biophysics Neurophysiology Biology Research and Analysis Methods General Biochemistry Genetics and Molecular Biology Membrane Structures 03 medical and health sciences Bacterial Proteins Escherichia coli Solid State Physics Sulfur Containing Amino Acids Molecular replacement Vesicles Cysteine Uptake system ktrab Molecular Biology Rck domain General Immunology and Microbiology Human bk channel Angstrom resolution Organic Chemistry Chemical Compounds Biology and Life Sciences Membrane Proteins Proteins Transporter Cell Biology 030104 developmental biology Membrane protein chemistry Trk receptor Liposomes Potassium Adenosine triphosphate Receptor desensitization Neuroscience |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP PLoS Biology PLoS Biology, Vol 14, Iss 1, p e1002356 (2016) 'PLoS Biology ', vol: 14, pages: e1002356-1-e1002356-21 (2016) |
| ISSN: | 1545-7885 |
| Popis: | KtrAB belongs to the Trk/Ktr/HKT superfamily of monovalent cation (K+ and Na+) transport proteins that closely resemble K+ channels. These proteins underlie a plethora of cellular functions that are crucial for environmental adaptation in plants, fungi, archaea, and bacteria. The activation mechanism of the Trk/Ktr/HKT proteins remains unknown. It has been shown that ATP stimulates the activity of KtrAB while ADP does not. Here, we present X-ray structural information on the KtrAB complex with bound ADP. A comparison with the KtrAB-ATP structure reveals conformational changes in the ring and in the membrane protein. In combination with a biochemical and functional analysis, we uncover how ligand-dependent changes in the KtrA ring are propagated to the KtrB membrane protein and conclude that, despite their structural similarity, the activation mechanism of KtrAB is markedly different from the activation mechanism of K+ channels. This study reveals how structural changes triggered by the exchange of bound ADP for ATP activate KtrAB, a potassium ion transporter involved in osmotic adaption in bacteria. Author Summary Animals have organs that regulate the balance of water and ions in the fluids bathing their cells. In contrast, the cells of plants, bacteria, and fungi have little or no control over those fluids and, thus, they have to cope with changes in the local environment. These cells have therefore evolved specific molecular systems that are crucial for environmental adaptation. We study the molecular properties of the membrane protein KtrAB—a member of the Trk/Ktr/HKT superfamily of transport proteins that shuffle K+ and Na+ ions across the plasma membrane, closely resemble K+ channels, and underlie environmental adaptation of cells of plants, fungi, bacteria, and archaea. KtrAB is formed by the KtrB membrane protein and the KtrA cytosolic ring protein. KtrA binds to both ADP and ATP, resulting in a low-activity ADP-bound state and a high-activity ATP-bound state, respectively. We determined a low resolution structure of a low-activity form of the transport protein. A comparison of this structure with the structure of ATP-bound KtrAB reveals changes in both the KtrA ring and the KtrB membrane protein. We uncover how changes in the KtrA ring are propagated to KtrB and conclude that, despite their structural similarity, the activation mechanism of KtrAB is markedly different from the activation mechanism of K+ channels. |
| Databáze: | OpenAIRE |
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