A computational investigation on the role of glycosylation in the binding of alpha1 nicotinic acetylcholine receptor with two alpha-neurotoxins
| Autor: | Georgios A. Spyroulias, Georgios A. Dalkas, Nikolaos Dimitropoulos, Konstantinos Poulas, Athanasios Papakyriakou, Christos T. Chasapis |
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| Rok vydání: | 2010 |
| Předmět: |
Glycosylation
In silico Protein subunit Neurotoxins Plasma protein binding Molecular Dynamics Simulation Receptors Nicotinic complex mixtures Biochemistry 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Protein structure Structural Biology Animals Humans Homology modeling Cobra Neurotoxin Proteins Molecular Biology 030304 developmental biology 0303 health sciences Chemistry Bungarotoxins Protein Structure Tertiary Nicotinic acetylcholine receptor Structural Homology Protein Ligand-gated ion channel 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Proteins: Structure, Function, and Bioinformatics; Vol 79 |
| ISSN: | 1097-0134 |
| Popis: | Based on the crystal structure of the extracellular domain (ECD) of the mouse nicotinic acetylcholine receptor (nAChR) alpha1 subunit bound to α-bungarotoxin (α-Btx) we have generated in silico models of the human nAChR α1 bound to α-Btx and α-cobratoxin (α-Cbtx), both in the presence and in the absence of the N-linked carbohydrate chain. To gain further insight into the structural role of glycosylation molecular dynamics (MD) simulations were carried out in explicit solvent so as to compare the conformational dynamics of the binding interface between nAChR α1 and the two toxins. An interesting observation during the course of the MD simulations is the strengthening of the receptor-toxin interaction in the presence of the carbohydrate chain, mediated through a shift in the position of the sugars towards the bound toxin. Critical protein-sugar interactions implicate residues Ser187 and Trp184 of nAChR and Thr6, Ser9, and Thr15 of α-Btx, as well as Thr6 and Pro7 of α-Cbtx. Analysis of the predicted residue-specific intermolecular interactions is intended to inspire biophysical studies on the functional role of glycosylation in the gating mechanism. |
| Databáze: | OpenAIRE |
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