A SINGLE HYDROPHOBIC TO HYDROPHOBIC SUBSTITUTION IN THE TRANSMEMBRANEDOMAIN IMPAIRS ASPARTATE RECEPTOR FUNCTION

Many transmembrane receptors, such as the insulin, EGF, and bacterial chemotaxis receptors, have only one or a few transmembrane domains con necting an extracellular ligand-binding domain to a cytoplasmic signal ing domain. The general belief is that the transmembrane domains in th ese receptors have no specific sequence requirements as long as they a re hydrophobic and long enough to span the membrane as an alpha-helix. To test this model, we constructed mutants in the aspartate receptor. This receptor is a dimer with two transmembrane domains per subunit. Amino acid substitutions can be made at several positions in the secon d transmembrane domain, which connects the periplasmic aspartate-bindi ng domain to the cytoplasmic signaling domain, and the receptor remain s functional. However, a single substitution of one hydrophobic residu e for another can impair receptor function in methylation and swarm pl ate assays. These results suggest that the second transmembrane domain may pack against the other transmembrane domains in the receptor and small changes in this packing can affect the function of the receptor.