Position-specific Asp-Lys pairing can affect signal sequence function and membrane protein topology.
Positively charged amino acids are major determinants of the topology of bacterial inner membrane proteins, whereas negatively charged residues by themselves have little or no influence on the transmembrane orientation. Further, positively charged amino acids can very efficiently block the function of signal sequences when placed immediately downstream, while negatively charged residues are much less potent also in this regard. Here, we show that a negatively charged aspartic acid situated close to a positively charged lysine can attenuate both of these effects in a position-specific manner, suggesting that intra- or intermolecular charge pairing can modulate the interactions between positively charged residues in the nascent chain and parts of the secretory machinery or membrane phospholipids. These observations further underscore the importance of charged amino acids during protein translocation and membrane protein assembly.
Andersson
H
H
Department of Molecular Biology, Karolinska Institute Center for Structural Biochemistry, NOVUM, Huddinge, Sweden.
von Heijne
G
G
D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000737:chemistry*; D004563:Electrochemistry; D010450:Endopeptidases / Q000378:metabolism; D008239:Lysine / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D021382:Protein Sorting Signals / Q000378:metabolism*; D012697:Serine Endopeptidases
D008565:Membrane Proteins; D021382:Protein Sorting Signals; D001224:Aspartic Acid; D010450:Endopeptidases; D012697:Serine Endopeptidases; C026515:type I signal peptidase; D008239:Lysine