Sub-Nanoscale Surface Ruggedness Provides a Water-Tight Seal for Exposed Regions in Soluble Protein Structure
| Autor: | Erica Patricia Schulz, Marisa Alejandra Frechero, Gustavo A. Appignanesi, Ariel Fernández |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Biophysics/Theory and Simulation
PROTEINS Otras Ciencias Biológicas Shell (structure) lcsh:Medicine Computational Biology/Macromolecular Structure Analysis 010402 general chemistry Bioinformatics 01 natural sciences Seal (mechanical) Physics/Interdisciplinary Physics purl.org/becyt/ford/1 [https] Ciencias Biológicas 03 medical and health sciences Protein structure WATER STRUCTURE Molecule purl.org/becyt/ford/1.6 [https] BIOLOGICAL WATER lcsh:Science 030304 developmental biology 0303 health sciences Multidisciplinary Hydrogen bond Chemistry Intermolecular force lcsh:R Biophysics/Structural Genomics Proteins Water Hydrogen Bonding 0104 chemical sciences Structural biology Solubility Chemical physics Thermodynamics Protein folding lcsh:Q CIENCIAS NATURALES Y EXACTAS Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 5, Iss 9 (2010) CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| ISSN: | 1932-6203 |
| Popis: | Soluble proteins must maintain backbone hydrogen bonds (BHBs) water-tight to ensure structural integrity. This protection is often achieved by burying the BHBs or wrapping them through intermolecular associations. On the other hand, water has low coordination resilience, with loss of hydrogen-bonding partnerships carrying significant thermodynamic cost. Thus, a core problem in structural biology is whether natural design actually exploits the water coordination stiffness to seal the backbone in regions that are exposed to the solvent. This work explores the molecular design features that make this type of seal operative, focusing on the side-chain arrangements that shield the protein backbone. We show that an efficient sealing is achieved by adapting the sub-nanoscale surface topography to the stringency of water coordination: an exposed BHB may be kept dry if the local concave curvature is small enough to impede formation of the coordination shell of a penetrating water molecule. Examination of an exhaustive database of uncomplexed proteins reveals that exposed BHBs invariably occur within such sub-nanoscale cavities in native folds, while this level of local ruggedness is absent in other regions. By contrast, BHB exposure in misfolded proteins occurs with larger local curvature promoting backbone hydration and consequently, structure disruption. These findings unravel physical constraints fitting a spatially dependent least-action for water coordination, introduce a molecular design concept, and herald the advent of water-tight peptide based materials with sufficient backbone exposure to remain flexible. © 2010 Schulz et al. Fil: Schulz, Erica Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina Fil: Frechero, Marisa Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina Fil: Appignanesi, Gustavo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina Fil: Fernández, Ariel. Rice University; Estados Unidos |
| Databáze: | OpenAIRE |
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