Mechanism and Structural Basis for Recognition of Signal Peptides
The Signal Hypothesis proposes that information for segregation of secretory proteins from cytoplasmic proteins is encoded within signal peptides by a highly specific structure or signal that binds to a receptor. However, to date, no specific signal has been identified within the sequence or conformation of signal peptides. Here, the effects of various structural alterations on signal peptide function are examined. More than 50 altered signal peptides were generated by incorporation of amino acid analogs during protein synthesis. Most of these structural changes of signal peptides did not block their function; only five cases were noted in which segregation of secretory proteins was impaired. The general conclusion from this study and from other available data is that signal peptides express only a low degree of structural specificity that is incompatible with their serving as ligands for a high-affinity receptor, as suggested in the Signal Hypothesis. A new model, termed the “Allosteric Model,” is presented to explain how signal peptides are recognized despite their considerable structural diversity.
KeywordsProline Leucine Phenylalanine Threonine Valine
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