Multiple Stable Conformations Account for Reversible Concentration‐Dependent Oligomerization and Autoinhibition of a Metamorphic Metallopeptidase |
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Authors: | Mar López‐Pelegrín Dr Núria Cerdà‐Costa Dr Anna Cintas‐Pedrola Fátima Herranz‐Trillo Dr Pau Bernadó Dr Juan R Peinado Dr Joan L Arolas Prof?Dr F Xavier Gomis‐Rüth |
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Institution: | 1. 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;2. Centre de Biochimie Structurale, INSERM U1054, CNRS UMR 5048, Université Montpellier 1 and 2, 29 rue de Navacelles, 34090 Montpellier (France);3. Present address: Department of Medical Sciences, University of Castilla‐La Mancha, 13071 Ciudad Real (Spain) |
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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. |
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Keywords: | metallopeptidases metamorphic proteins protein folding protein structures |
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