title: Staphylokinase Displays Surprisingly Low Mechanical Stability.
abstract: Single-molecule force spectroscopy (SMFS) and molecular dynamics (MD) simulations have revealed that shear topology is an important structural feature for mechanically stable proteins. Proteins containing a β-grasp fold display the typical shear topology and are generally of significant mechanical stability. In an effort to experimentally identify mechanically strong proteins using single-molecule atomic force microscopy, we found that staphylokinase (SAK), which has a typical β-grasp fold and was predicted to be mechanically stable in coarse-grained MD simulations, displays surprisingly low mechanical stability. At a pulling speed of 400 nm/s, SAK unfolds at ∼60 pN, making it the mechanically weakest protein among the β-grasp fold proteins that have been characterized experimentally. In contrast, its structural homologous protein streptokinase β domain displays significant mechanical stability under the same experimental condition. Our results showed that the large malleability of native-state SAK is largely responsible for its low mechanical stability. The molecular origin of this large malleability of SAK remains unknown. Our results reveal a hidden complexity in protein mechanics and call for a detailed investigation into the molecular determinants of the protein mechanical malleability.
authors.affiliation: Department of Chemistry, University of British Columbia , Vancouver, BC V6T 1Z1, Canada.
authors.forename: Chengzhi
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Chemistry, University of British Columbia , Vancouver, BC V6T 1Z1, Canada.
authors.forename: Hongbin
authors.identifier: 0000-0001-7813-1332
authors.initials: H
authors.lastname: Li
mesh_terms: D001696:Biomechanical Phenomena; D004795:Enzyme Stability; D055595:Mechanical Phenomena; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D000072757:Protein Conformation, beta-Strand; D000072417:Protein Domains; D058767:Protein Unfolding; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D012997:Solvents; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus