Positively charged amino acid residues can act as topogenic determinants in membrane proteins.

Publisher Website
Google Scholar
Abstract
When alkaline phosphatase is fused to the periplasmic domain of a cytoplasmic membrane prtein, it is efficiently exported to the periplasm. Such a hybrid protein exhibits high alkaline phosphatase enzymatic activity. When alkaline phosphatase is fused to the cytoplasmic domain of a membrane protein, it remains, for the most part, in the cytoplasm. Such fusions exhibit low enzymatic activity. However, stable retention of alkaline phosphatase in the cytoplasm requires the presence in the fusion protein of the cytoplsmic loop ordinarily present in that position in the native, unfused protein. Using oligonucleotid-directed mutagenesis, we have shown that positively charged amino acids are required for the stable cytoplasmic localization of the fused alkaline phosphatase. We propose that, in addition to hydrophobic transmembrane segments, positvely charged amino acids in the hydrophilic cytoplasmic domains of a membrane protein''s topology.