Structural insights into conformational changes of a cyclic nucleotide-binding domain in solution from Mesorhizobium loti K1 channel
| Autor: | Matthias Stoldt, Sven Schünke, Dieter Willbold, Justin Lecher, Ulrich Benjamin Kaupp |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Multidisciplinary
biology Stereochemistry Chemistry Allosteric regulation Cyclic Nucleotide-Gated Cation Channels Gating Nuclear magnetic resonance spectroscopy Biological Sciences Crystallography X-Ray biology.organism_classification Protein Structure Tertiary Mesorhizobium loti Protein structure Cyclic nucleotide-binding domain Mutation Cyclic AMP Cyclic nucleotide-gated ion channel Nuclear Magnetic Resonance Biomolecular Ion channel Alphaproteobacteria |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1015890108 |
| Popis: | Cyclic nucleotide-sensitive ion channels, known as HCN and CNG channels, are activated by binding of ligands to a domain (CNBD) located on the cytoplasmic side of the channel. The underlying mechanisms are not well understood. To elucidate the gating mechanism, structures of both the ligand-free and -bound CNBD are required. Several crystal structures of the CNBD from HCN2 and a bacterial CNG channel (MloK1) have been solved. However, for HCN2, the cAMP-free and -bound state did not reveal substantial structural rearrangements. For MloK1, structural information for the cAMP-free state has only been gained from mutant CNBDs. Moreover, in the crystal, the CNBD molecules form an interface between dimers, proposed to be important for allosteric channel gating. Here, we have determined the solution structure by NMR spectroscopy of the cAMP-free wild-type CNBD of MloK1. A comparison of the solution structure of cAMP-free and -bound states reveals large conformational rearrangement on ligand binding. The two structures provide insights on a unique set of conformational events that accompany gating within the ligand-binding site. |
| Databáze: | OpenAIRE |
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