TY - JOUR
T1 - Preprotein mature domains contain translocase targeting signals that are essential for secretion
AU - Chatzi, Katerina E.
AU - Sardis, Marios Frantzeskos
AU - Tsirigotaki, Alexandra
AU - Koukaki, Marina
AU - Šoštarić, Nikolina
AU - Konijnenberg, Albert
AU - Sobott, Frank
AU - Kalodimos, Charalampos G.
AU - Karamanou, Spyridoula
AU - Economou, Anastassios
N1 - Publisher Copyright:
© 2017 Chatzi et al.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Secretory proteins are only temporary cytoplasmic residents. They are typically synthesized as preproteins, carrying signal peptides N-terminally fused to their mature domains. In bacteria secretion largely occurs posttranslationally through the membrane-embedded SecA-SecYEG translocase. Upon crossing the plasma membrane, signal peptides are cleaved off and mature domains reach their destinations and fold. Targeting to the translocase is mediated by signal peptides. The role of mature domains in targeting and secretion is unclear. We now reveal that mature domains harbor their own independent targeting signals (mature domain targeting signals [MTSs]). These are multiple, degenerate, interchangeable, linear or 3D hydrophobic stretches that become available because of the unstructured states of targeting- competent preproteins. Their receptor site on the cytoplasmic face of the SecYEG-bound SecA is also of hydrophobic nature and is located adjacent to the signal peptide cleft. Both the preprotein MTSs and their receptor site on SecA are essential for protein secretion. Evidently, mature domains have their own previously unsuspected distinct roles in preprotein targeting and secretion.
AB - Secretory proteins are only temporary cytoplasmic residents. They are typically synthesized as preproteins, carrying signal peptides N-terminally fused to their mature domains. In bacteria secretion largely occurs posttranslationally through the membrane-embedded SecA-SecYEG translocase. Upon crossing the plasma membrane, signal peptides are cleaved off and mature domains reach their destinations and fold. Targeting to the translocase is mediated by signal peptides. The role of mature domains in targeting and secretion is unclear. We now reveal that mature domains harbor their own independent targeting signals (mature domain targeting signals [MTSs]). These are multiple, degenerate, interchangeable, linear or 3D hydrophobic stretches that become available because of the unstructured states of targeting- competent preproteins. Their receptor site on the cytoplasmic face of the SecYEG-bound SecA is also of hydrophobic nature and is located adjacent to the signal peptide cleft. Both the preprotein MTSs and their receptor site on SecA are essential for protein secretion. Evidently, mature domains have their own previously unsuspected distinct roles in preprotein targeting and secretion.
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U2 - 10.1083/jcb.201609022
DO - 10.1083/jcb.201609022
M3 - Article
C2 - 28404644
AN - SCOPUS:85020748698
SN - 0021-9525
VL - 216
SP - 1357
EP - 1369
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 5
ER -