Domain swapping dissection in Thermotoga maritima arginine binding protein: How structural flexibility may compensate destabilization(70 visite) Smaldone G, Berisio R, Balasco N, D'Auria S, Vitagliano L, Ruggiero A
Bba-Bioenergetics (ISSN: 1570-9639print, 1570-9639linking, 0005-2728), 2018 May 31; 1866(9): 952-962.
Tipo di articolo: Journal Article,
Impact factor: 2.773, Impact factor a 5 anni: 2.751
Url: Non disponibile.
Parole chiave: Argininemia Diagnosis, Biosensors, Calorimetry, Domain Swapping, Protein Structure-Stability,
*** IBB - CNR *** IRCCS SDN, 80143 Napoli, Italy., Institute of Biostructures and Bioimaging, CNR, Via Mezzocannone 16, I-80134 Napoli, Italy., Institute of Food Science, CNR, Via Roma, 64 Avellino, Italy., Institute of Biostructures and Bioimaging, CNR, Via Mezzocannone 16, I-80134 Napoli, Italy. Electronic address: email@example.com., Institute of Biostructures and Bioimaging, CNR, Via Mezzocannone 16, I-80134 Napoli, Italy. Electronic address: firstname.lastname@example.org.,
Thermotoga 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 (TmArgBP(20-233)) 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 TmArgBP(20-233) 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 TmArgBP(20-233) stability whereas it barely affects its ligand-free state. The crystallographic structures of these forms provide a rationale to this puzzling observation. Indeed, the arginine-bound state is very rigid and virtually unchanged upon protein truncation. On the other hand, the flexible ligand-free TmArgBP(20-233) is able to adopt a novel state as a consequence of the helix deletion. Therefore, the flexibility of the ligand-free form endows this state with a remarkable robustness upon severe perturbations. In this scenario, TmArgBP dissection highlights an intriguing connection between destabilizing/stabilizing effects and the overall flexibility that could operate also in other proteins.
82 Records (78 escludendo Abstract e Conferenze). Impact factor totale: 291.605 (290.237 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 303.122 (301.81 escludendo Abstract e Conferenze).