Analysis of the Open and Closed Conformations of the GTP-binding Protein YsxC from Bacillus subtilis

• Published in: Journal of molecular biology Vol. 339; no. 2; pp. 265 - 278
• Main Authors: Ruzheinikov, Sergey N., Das, Sanjan K., Sedelnikova, Svetlana E., Baker, Patrick J., Artymiuk, Peter J., Garcı́a-Lara, Jorge, Foster, Simon J., Rice, David W.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 28-05-2004
• Subjects: Amino Acid Sequence; Bacillus subtilis; Bacillus subtilis - chemistry; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; GTP; GTP-binding protein; GTP-Binding Proteins - chemistry; GTP-Binding Proteins - metabolism; GTPase; Guanosine Triphosphate - chemistry; Hydrolysis; Models, Molecular; Molecular Sequence Data; Protein Conformation; Sequence Homology, Amino Acid; YsxC; GTP-binding protein; GTP; Bacillus subtilis; TRAFAC, translation factor related; GTPase; YsxC
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2004.03.043

Genetic analysis has suggested that the product of the
Bacillus subtilis ysxC gene is essential for survival of the microorganism and hence may represent a target for the development of a novel anti-infective agent.
B.
subtilis
YsxC is a member of the translation factor related class of GTPases and its crystal structure has been determined in an apo form and in complex with GDP and GMPPNP/Mg
2+. Analysis of these structures has allowed us to examine the conformational changes that occur during the process of nucleotide binding and GTP hydrolysis. These structural changes particularly affect parts of the switch I and switch II region of YsxC, which become ordered and disordered, respectively in the “closed” or “on” GTP-bound state and disordered and ordered, respectively, in the “open” or “off” GDP-bound conformation. Finally, the binding of the magnesium cation results in subtle shifts of residues in the G3 region, at the start of switch II, which serve to optimize the interaction with a key aspartic acid residue. The structural flexibility observed in YsxC is likely to contribute to the role of the protein, possibly allowing transduction of an essential intracellular signal, which may be mediated
via interactions with a conserved patch of surface-exposed, basic residues that lies adjacent to the GTP-binding site.