Signal sequences initiate the pathway of maturation in the endoplasmic reticulum lumen.
An interaction between an N-terminal signal sequence and the translocon leads to the initiation of protein translocation into the endoplasmic reticulum lumen. Subsequently, folding and modification of the substrate rapidly ensue. The close temporal coordination of these processes suggests that they may be structurally and functionally coordinated as well. Here we show that information encoded in the hydrophobic domain of a signal sequence influences the timing and efficiency of at least two steps in maturation, namely N-linked glycosylation and signal sequence cleavage. We demonstrate that these consequences correlate with and likely stem from the nature of the initial association made between the signal sequence and the translocon during the initiation of translocation. We propose a model by which these maturational events are controlled by the signal sequence-translocon interaction. Our work demonstrates that the pathway taken by a nascent chain through post-translational maturation depends on information encoded in its signal sequence.
Rutkowski
D Thomas
DT
Department of Biochemistry and Biophysics, University of California, San Francisco, 94143, USA.
Ott
Carolyn M
CM
Polansky
Jon R
JR
Lingappa
Vishwanath R
VR
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D003432:Cross-Linking Reagents / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006031:Glycosylation; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D011487:Protein Conformation; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014357:Trypsin / Q000494:pharmacology
D003432:Cross-Linking Reagents; D018076:DNA, Complementary; D021382:Protein Sorting Signals; D014357:Trypsin