Domain swapping dissection in Thermotoga maritima arginine binding protein: How structural flexibility may compensate destabilization

Publication date: September 2018Source: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Volume 1866, Issue 9Author(s): Giovanni Smaldone, Rita Berisio, Nicole Balasco, Sabato D'Auria, Luigi Vitagliano, Alessia RuggieroAbstractThermotoga maritima Arginine Binding Protein (TmArgBP) is a valuable candidate for arginine biosensing in diagnostics. This protein is endowed with unusual structural properties that include an extraordinary thermal/chemical stability, a domain swapped structure that undergoes large tertiary and quaternary structural transition, and the ability to form non-canonical oligomeric species. As the intrinsic stability of TmArgBP allows for extensive protein manipulations, we here dissected its structure in two parts: its main body deprived of the swapping fragment (TmArgBP20-233) and the C-terminal peptide corresponding to the helical swapping element. Both elements have been characterized independently or in combination using a repertoire of biophysical/structural techniques. Present investigations clearly indicate that TmArgBP20-233 represents a better scaffold for arginine sensing compared to the wild-type protein. Moreover, our data demonstrate that the ligand-free and the ligand-bound forms respond very differently to this helix deletion. This drastic perturbation has an important impact on the ligand-bound form of TmArgBP20-233 stability whereas it barely affects its ligand-free state. The crystallographic structures of these forms provide...

Source: Biochimica et Biophysica Acta (BBA) Proteins and Proteomics - July 11, 2018 Category: Biochemistry Source Type: research