Faculty Collaboration Database

The NMR solution structure of BeF(3)(-)-activated Spo0F reveals the conformational switch in a phosphorelay system. J Mol Biol 2003 Aug 01;331(1):245-54

Date

07/24/2003

Pubmed ID

12875849

DOI

10.1016/s0022-2836(03)00733-2

Scopus ID

2-s2.0-0037485779 (requires institutional sign-in at Scopus site)   37 Citations

Abstract

Two-component systems, which are comprised of a single histidine-aspartate phosphotransfer module, are the dominant signaling pathways in bacteria and have recently been identified in several eukaryotic organisms as well. A tandem connection of two or more histidine-aspartate motifs forms complex phosphorelays. While response regulators from simple two-component systems have been characterized structurally in their inactive and active forms, we address here the question of whether a response regulator from a phosphorelay has a distinct structural basis of activation. We report the NMR solution structure of BeF(3)(-)-activated Spo0F, the first structure of a response regulator from a phosphorelay in its activated state. Conformational changes were found in regions previously identified to change in simple two-component systems. In addition, a downward shift by half a helical turn in helix 1, located on the opposite side of the common activation surface, was observed as a consequence of BeF(3)(-) activation. Conformational changes in helix 1 can be rationalized by the distinct function of phosphoryl transfer to the second histidine kinase, Spo0B, because helix 1 is known to interact directly with Spo0B and the phosphatase RapB. The identification of structural rearrangements in Spo0F supports the hypothesis of a pre-existing equilibrium between the inactive and active state prior to phosphorylation that was suggested on the basis of previous NMR dynamics studies on Spo0F. A shift of a pre-existing equilibrium is likely a general feature of response regulators.

Author List

Gardino AK, Volkman BF, Cho HS, Lee SY, Wemmer DE, Kern D

Author

Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aspartic Acid
Bacillus subtilis
Bacterial Proteins
Beryllium
Fluorides
Histidine
Models, Molecular
Nuclear Magnetic Resonance, Biomolecular
Phosphorylation
Phosphotransferases
Protein Conformation
Signal Transduction