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Updated: Apr 25, 2026

X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050
Published on: May 13, 2020
Multiple stable conformations account for reversible concentration-dependent oligomerization and autoinhibition of a
Mar López-Pelegrín1, Núria Cerdà-Costa, Anna Cintas-Pedrola
1Proteolysis 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.
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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