title: Bidirectional Transformation of a Metamorphic Protein between the Water-Soluble and Transmembrane Native States.
abstract: The bidirectional transformation of a protein between its native water-soluble and integral transmembrane conformations is demonstrated for FraC, a hemolytic protein of the family of pore-forming toxins. In the presence of biological membranes, the water-soluble conformation of FraC undergoes a remarkable structural reorganization generating cytolytic transmembrane nanopores conducive to cell death. So far, the reverse transformation from the native transmembrane conformation to the native water-soluble conformation has not been reported. We describe the use of detergents with different physicochemical properties to achieve the spontaneous conversion of transmembrane pores of FraC back into the initial water-soluble state. Thermodynamic and kinetic stability data suggest that specific detergents cause an asymmetric change in the energy landscape of the protein, allowing the bidirectional transformation of a membrane protein.
authors.affiliation: Department of Chemistry and Biotechnology and ‡Department of Bioengineering, School of Engineering, The University of Tokyo , Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Chemistry and Biotechnology and ‡Department of Bioengineering, School of Engineering, The University of Tokyo , Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Jose M M
authors.initials: JM
authors.lastname: Caaveiro
authors.affiliation: Department of Chemistry and Biotechnology and ‡Department of Bioengineering, School of Engineering, The University of Tokyo , Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Tsumoto
mesh_terms: D000818:Animals; D003064:Cnidarian Venoms / Q000737:chemistry*; D003902:Detergents; D055767:Immobilized Proteins / Q000737:chemistry; D008958:Models, Molecular; D058608:Nanopores; D011487:Protein Conformation; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D012995:Solubility; D013816:Thermodynamics; D014867:Water
chemical_list: D003064:Cnidarian Venoms; D003902:Detergents; D055767:Immobilized Proteins; C545670:fragaceatoxin C; D014867:Water