Forced unfolding of the fibronectin type III module reveals a tensile molecular recognition switch
| Autor: | Viola Vogel, Hui Lu, André Krammer, Barry Isralewitz, Klaus Schulten |
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| Rok vydání: | 1999 |
| Předmět: |
Models
Molecular Integrins Protein Denaturation Protein Folding Protein Conformation Integrin Crystallography X-Ray Antiparallel (biochemistry) Protein Structure Secondary Protein structure Molecular recognition Tensile Strength Computer Simulation Amino Acid Sequence Disulfides Cell adhesion Integrin binding Binding Sites Multidisciplinary biology Chemistry Hydrogen Bonding Biological Sciences Fibronectins Protein Structure Tertiary Fibronectin Crystallography biology.protein Protein folding Oligopeptides Software |
| Zdroj: | Proceedings of the National Academy of Sciences. 96:1351-1356 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | The 10th type III module of fibronectin possesses a β -sandwich structure consisting of seven β -strands (A–G) that are arranged in two antiparallel sheets. It mediates cell adhesion to surfaces via its integrin binding motif, Arg 78 , Gly 79 , and Asp 80 (RGD), which is placed at the apex of the loop connecting β -strands F and G. Steered molecular dynamics simulations in which tension is applied to the protein’s terminal ends reveal that the β -strand G is the first to break away from the module on forced unfolding whereas the remaining fold maintains its structural integrity. The separation of strand G from the remaining fold results in a gradual shortening of the distance between the apex of the RGD-containing loop and the module surface, which potentially reduces the loop’s accessibility to surface-bound integrins. The shortening is followed by a straightening of the RGD-loop from a tight β -turn into a linear conformation, which suggests a further decrease of affinity and selectivity to integrins. The RGD-loop therefore is located strategically to undergo strong conformational changes in the early stretching stages of the module and thus constitutes a mechanosensitive control of ligand recognition. |
| Databáze: | OpenAIRE |
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