title: Molecular gymnastics: serpin structure, folding and misfolding.
abstract: The native state of serpins represents a long-lived intermediate or metastable structure on the serpin folding pathway. Upon interaction with a protease, the serpin trap is sprung and the molecule continues to fold into a more stable conformation. However, thermodynamic stability can also be achieved through alternative, unproductive folding pathways that result in the formation of inactive conformations. Our increasing understanding of the mechanism of protease inhibition and the dynamics of native serpin structures has begun to reveal how evolution has harnessed the actual process of protein folding (rather than the final folded outcome) to elegantly achieve function. The cost of using metastability for function, however, is an increased propensity for misfolding.
authors.affiliation: Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, Clayton Campus, Melbourne 3800, Australia. james.whisstock@med.monash.edu.au
authors.forename: James C
authors.initials: JC
authors.lastname: Whisstock
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Bottomley
mesh_terms: D000818:Animals; D029681:Arabidopsis Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008958:Models, Molecular; D015394:Molecular Structure; D046912:Multiprotein Complexes; D011487:Protein Conformation; D017510:Protein Folding; D015843:Serpins / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics; D013975:Thyroxine-Binding Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D029681:Arabidopsis Proteins; D046912:Multiprotein Complexes; D015843:Serpins; D013975:Thyroxine-Binding Proteins