Structure and dynamics of transmembrane signaling by the Escherichia coli aspartate receptor.

The structure of the cytosolic extension of the first transmembrane region (TM1) of the Escherichia coli aspartate receptor (residues 3, 4, and 5) and conformational changes within that region have been characterized by targeted cross-linking studies and by measurement of the effect of aspartate binding on cross-linking and methylation rates and compared with the periplasmic extension of the same helix. These experiments show that (1) the cytosolic extension of TM1 is helical, with residues 4 and 4' closest together at the dimer interface; (2) the helix is more solvent-exposed at the cytosolic side of the membrane than on the periplasmic side; and (3) aspartate binding enhances the rate of cross-linking at Cys 4, and the resulting cross-linked receptor displays aspartate-induced transmembrane increases in methylation by the cytoplasmic methylase (the CheR protein). We conclude that aspartate induces a conformational change that does not involve large intersubunit movements that lead to an increase in distance between the cytosolic ends of the first membrane-spanning helices; rather, the motion involved is largely contained within individual subunits, possibly resulting in a small movement between positions 4 and 4'.