Proline Restricts Loop I Conformation of the High Affinity WW Domain from Human Nedd4-1 to a Ligand Binding-Competent Type I β-Turn
| Autor: | Dieter Willbold, Andrew J. Dingley, Marianne Schulte, Stefan Freischem, Vineet Panwalkar |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
chemistry.chemical_classification
Binding Sites biology Proline Stereochemistry Protein Conformation Nedd4 Ubiquitin Protein Ligases NEDD4 Sequence alignment Peptide Molecular Dynamics Simulation Ligand (biochemistry) Ligands Surfaces Coatings and Films WW domain Protein structure chemistry Materials Chemistry biology.protein Humans Physical and Theoretical Chemistry Binding site |
| Zdroj: | The journal of physical chemistry. B. 122(15) |
| ISSN: | 1520-5207 |
| Popis: | Sequence alignment of the four WW domains from human Nedd4-1 (neuronal precursor cell expressed developmentally down-regulated gene 4-1) reveals that the highest sequence diversity exists in loop I. Three residues in this type I β-turn interact with the PPxY motif of the human epithelial Na+ channel (hENaC) subunits, indicating that peptide affinity is defined by the loop I sequence. The third WW domain (WW3*) has the highest ligand affinity and unlike the other three hNedd4-1 WW domains or other WW domains studied contains the highly statistically preferred proline at the (i + 1) position found in β-turns. In this report, molecular dynamics simulations and experimental data were combined to characterize loop I stability and dynamics. Exchange of the proline to the equivalent residue in WW4 (Thr) results in the presence of a predominantly open seven residue Ω loop rather than the type I β-turn conformation for the wild-type apo-WW3*. In the presence of the ligand, the structure of the mutated loop I is lo... |
| Databáze: | OpenAIRE |
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