Transmembrane signalling and the aspartate receptor.
BACKGROUND
The aspartate receptor is a transmembrane protein that mediates bacterial chemotaxis. The structures of the periplasmic ligand-binding domain reveal a dimer, each subunit with four alpha-helix bundles, with aspartate binding to one of two sites at the subunit interface. The transmembrane regions of the receptor were not included in these structures.


RESULTS
To investigate the structure of the transmembrane region, we have made a mutant protein with two cross-links, restraining the subunit-subunit interface on both sides of the membrane, and have made an energy-minimized model of the transmembrane region. We demonstrate that the transmembrane helices form a coiled coil which extends from the periplasmic subunit through the membrane. We have constructed a model of the ligand-binding domains with the amino-terminal transmembrane helices.


CONCLUSIONS
We draw three conclusions from our model. Firstly, the interface between receptor subunits in the intact receptor consists of an uninterrupted coiled coil. Secondly, this structure rules out several postulated mechanisms of signalling. Thirdly, side chain packing constraints within the helices dictate that local structural changes must be small, but are propagated over a long distance rather than being dissipated locally. Low energy changes in the conformation of side chains are a probable mechanism of signal transduction in the aspartate receptor.
Scott
W G
WG
MRC Laboratory of Molecular Biology, Cambridge, UK.
Stoddard
B L
BL
D000595:Amino Acid Sequence; D001224:Aspartic Acid; D018407:Bacterial Physiological Phenomena; D001665:Binding Sites; D002462:Cell Membrane / Q000502:physiology; D002633:Chemotaxis; D003196:Computer Graphics; D003432:Cross-Linking Reagents; D003545:Cysteine; D046911:Macromolecular Substances; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D017433:Protein Structure, Secondary; D017459:Receptors, Amino Acid / Q000737:chemistry* / Q000502:physiology; D012436:S-Adenosylmethionine; D015398:Signal Transduction; D012984:Software
D003432:Cross-Linking Reagents; D046911:Macromolecular Substances; D017459:Receptors, Amino Acid; C031959:aspartic acid receptor; D001224:Aspartic Acid; D012436:S-Adenosylmethionine; D003545:Cysteine