title: A single hydrophobic to hydrophobic substitution in the transmembrane domain impairs aspartate receptor function.
abstract: Many transmembrane receptors, such as the insulin, EGF, and bacterial chemotaxis receptors, have only one or a few transmembrane domains connecting an extracellular ligand-binding domain to a cytoplasmic signaling domain. The general belief is that the transmembrane domains in these receptors have no specific sequence requirements as long as they are 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 second transmembrane domain, which connects the periplasmic aspartate-binding domain to the cytoplasmic signaling domain, and the receptor remains functional. However, a single substitution of one hydrophobic residue for another can impair receptor function in methylation and swarm plate 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.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley 94720.
authors.forename: C J
authors.initials: CJ
authors.lastname: Jeffery
authors.forename: D E
authors.initials: DE
authors.lastname: Koshland
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics; D008745:Methylation; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010649:Phenylalanine / Q000235:genetics; D017433:Protein Structure, Secondary; D017459:Receptors, Amino Acid / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D017459:Receptors, Amino Acid; C031959:aspartic acid receptor; D010649:Phenylalanine