6GGP

Structure of the ligand-free form of truncated ArgBP (residues 20-233) from T. maritima

Summary for 6GGP

• Entry DOI: 10.2210/pdb6ggp/pdb
• Descriptor: Amino acid ABC transporter, periplasmic amino acid-binding protein (2 entities in total)
• Functional Keywords: domain swapping, biosensors, argininemia diagnosis, protein structure-stability, calorimetry., transport protein
• Biological source: Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
• Total number of polymer chains: 1
• Total formula weight: 23443.83

Authors

Smaldone, G.,Berisio, R.,Balasco, N.,D'Auria, S.,Vitagliano, L.,Ruggiero, A. (deposition date: 2018-05-03, release date: 2018-06-13, Last modification date: 2024-01-17)

Primary citation

Smaldone, G.,Berisio, R.,Balasco, N.,D'Auria, S.,Vitagliano, L.,Ruggiero, A.
Domain swapping dissection in Thermotoga maritima arginine binding protein: How structural flexibility may compensate destabilization.
Biochim. Biophys. Acta, 1866:952-962, 2018

PubMed Abstract: 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) 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 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 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 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.

PubMed: 29860047
DOI: 10.1016/j.bbapap.2018.05.016

Experimental method

X-RAY DIFFRACTION (1.03 Å)