title: How the serpin α1-proteinase inhibitor folds.
abstract: Serpins are remarkable and unique proteins in being able to spontaneously fold into a metastable conformation without the aid of a chaperone or prodomain. This metastable conformation is essential for inhibition of proteinases, so that massive serpin conformational change, driven by the favorable energetics of relaxation of the metastable conformation to the more stable one, can kinetically trap the proteinase-serpin acylenzyme intermediate. Failure to direct folding to the metastable conformation would lead to inactive, latent serpin. How serpins fold into such a metastable state is unknown. Using the ability of component peptides from the serpin α(1)PI to associate, we have now elucidated the pathway by which this serpin efficiently folds into its metastable state. In addition we have established the likely structure of the polymerogenic intermediate of the Z variant of α(1)PI.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
authors.forename: Klavs
authors.initials: K
authors.lastname: Dolmer
authors.forename: Peter G W
authors.initials: PG
authors.lastname: Gettins
mesh_terms: D019943:Amino Acid Substitution; D007700:Kinetics; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry; D010084:Oxidation-Reduction; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000737:chemistry; D017510:Protein Folding; D055503:Protein Multimerization; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D000515:alpha 1-Antitrypsin / Q000737:chemistry* / Q000235:genetics
chemical_list: D050505:Mutant Proteins; D010446:Peptide Fragments; D000515:alpha 1-Antitrypsin; D010196:Pancreatic Elastase