title: Multiple stable conformations account for reversible concentration-dependent oligomerization and autoinhibition of a metamorphic metallopeptidase.
abstract: Molecular plasticity controls enzymatic activity: the native fold of a protein in a given environment is normally unique and at a global free-energy minimum. Some proteins, however, spontaneously undergo substantial fold switching to reversibly transit between defined conformers, the "metamorphic" proteins. Here, we present a minimal metamorphic, selective, and specific caseinolytic metallopeptidase, selecase, which reversibly transits between several different states of defined three-dimensional structure, which are associated with loss of enzymatic activity due to autoinhibition. The latter is triggered by sequestering the competent conformation in incompetent but structured dimers, tetramers, and octamers. This system, which is compatible with a discrete multifunnel energy landscape, affords a switch that provides a reversible mechanism of control of catalytic activity unique in nature.
authors.affiliation: Proteolysis Lab, Molecular Biology Institute of Barcelona, CSIC, Barcelona Science Park c/Baldiri Reixac, 15-21, 08028 Barcelona (Spain) http://www.ibmb.csic.es/home/xgomis.
authors.forename: Mar
authors.initials: M
authors.lastname: López-Pelegrín
authors.forename: Núria
authors.initials: N
authors.lastname: Cerdà-Costa
authors.forename: Anna
authors.initials: A
authors.lastname: Cintas-Pedrola
authors.forename: Fátima
authors.initials: F
authors.lastname: Herranz-Trillo
authors.forename: Pau
authors.initials: P
authors.lastname: Bernadó
authors.forename: Juan R
authors.initials: JR
authors.lastname: Peinado
authors.forename: Joan L
authors.initials: JL
authors.lastname: Arolas
authors.forename: F Xavier
authors.initials: FX
authors.lastname: Gomis-Rüth
mesh_terms: D045726:Metalloproteases / Q000737:chemistry* / Q000378:metabolism; D063747:Methanocaldococcus / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D055503:Protein Multimerization; D055550:Protein Stability; D013816:Thermodynamics
chemical_list: D045726:Metalloproteases
keywords: metallopeptidases; metamorphic proteins; protein folding; protein structures