Perplexing cooperative folding and stability of a low-sequence complexity, polyproline 2 protein lacking a hydrophobic core
| Autor: | Joshua A. Riback, Zachary P. Gates, Michael C. Baxa, Benoît Roux, Wookyung Yu, Tobin R. Sosnick, Hui Li, Stephen B. H. Kent |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Models Molecular Protein Folding Glycine Gene Expression Cooperativity Dihedral angle 010402 general chemistry Crystallography X-Ray 01 natural sciences Protein Structure Secondary Arthropod Proteins 03 medical and health sciences Antifreeze protein Antifreeze Proteins Lattice protein Side chain Native state Animals Protein Interaction Domains and Motifs Amino Acid Sequence Polyproline helix Multidisciplinary Sequence Homology Amino Acid Chemistry Protein Stability Hydrogen Bonding Biological Sciences Recombinant Proteins 0104 chemical sciences Crystallography Kinetics 030104 developmental biology Siphonaptera Thermodynamics Protein folding Peptides Hydrophobic and Hydrophilic Interactions Sequence Alignment |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 114(9) |
| ISSN: | 1091-6490 |
| Popis: | The burial of hydrophobic side chains in a protein core generally is thought to be the major ingredient for stable, cooperative folding. Here, we show that, for the snow flea antifreeze protein (sfAFP), stability and cooperativity can occur without a hydrophobic core, and without α-helices or β-sheets. sfAFP has low sequence complexity with 46% glycine and an interior filled only with backbone H-bonds between six polyproline 2 (PP2) helices. However, the protein folds in a kinetically two-state manner and is moderately stable at room temperature. We believe that a major part of the stability arises from the unusual match between residue-level PP2 dihedral angle bias in the unfolded state and PP2 helical structure in the native state. Additional stabilizing factors that compensate for the dearth of hydrophobic burial include shorter and stronger H-bonds, and increased entropy in the folded state. These results extend our understanding of the origins of cooperativity and stability in protein folding, including the balance between solvent and polypeptide chain entropies. |
| Databáze: | OpenAIRE |
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