The folding of an immunoglobulin-like Greek key protein is defined by a common-core nucleus and regions constrained by topology
| Autor: | Stefan J. Hamill, Annette Steward, Jane Clarke |
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| Rok vydání: | 2000 |
| Předmět: |
Models
Molecular Protein Denaturation Protein Folding Amino Acid Motifs Protein Renaturation Immunoglobulins Fibronectin type III domain Topology Protein Structure Secondary Protein structure Structural Biology medicine Humans Molecular Biology Chemistry Tenascin Protein engineering Hydrogen-Ion Concentration Contact order Peptide Fragments Protein Structure Tertiary Folding (chemistry) Crystallography Kinetics medicine.anatomical_structure Mutation Mutagenesis Site-Directed Thermodynamics Protein folding Protein topology Nucleus |
| Zdroj: | Journal of molecular biology. 297(1) |
| ISSN: | 0022-2836 |
| Popis: | TNfn3, the third fibronectin type III domain of human tenascin, is an immunoglobulin-like protein that is a good model for experimental and theoretical analyses of Greek key folding. The third fibronectin type III domain of human tenascin folds and unfolds in a two-state fashion over a range of temperature and pH values, and in the presence of stabilising salts. Here, we present a high resolution protein engineering analysis of the single rate determining transition state. The 48 mutations report on the contribution of side-chains at 32 sites in the core and loop regions. Three areas in the protein exhibit high Phi-values, indicating that they are partially structured in the transition state. First, a common-core ring of four positions in the central strands B, C, E and F, that are in close contact, form a nucleus of tertiary interactions. The two other regions that appear well-formed are the C' region and the E-F loop. The Phi-values gradually decrease away from these regions such that the very ends of the two terminal strands A and G, have Phi-values of zero. We propose a model for the folding of immunoglobulin-like proteins in which the common-core "ring" forms the nucleus for folding, whilst the C' and E-F regions are constrained by topology to pack early. Folding characteristics of a group of structurally related proteins appear to support this model. |
| Databáze: | OpenAIRE |
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