Signal peptides are allosteric activators of the protein translocase.
Signal peptides are allosteric activators of the protein translocase.
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作者：
胞质外多肽通常合成为携带氨基末端可裂解信号肽的“前蛋白”，并通过移位酶分泌穿过膜。主要的细菌移位酶包括SecYEG蛋白传导通道和外周ATP酶马达SecA。大多数被分配到周质和周质以外的蛋白质都是由SecA在细胞分裂后输出的。前蛋白靶向SecA被认为涉及信号肽和分子伴侣，如SecB。在这里，我们揭示了信号肽具有超越靶向的新作用：它们是转位酶的重要变构激活剂。在对接在SecA上的它们的结合沟上时，信号肽反式作用以驱动三个连续的状态：首先，“触发”，其驱动移位酶至较低活化能状态;然后“捕获”，其接合在分泌装置上以高亲和力对接的非天然前蛋白成熟结构域，并且最后，“分泌”，在此期间捕获的成熟结构域在片段中经历多次易位周转。成熟结构域的显著贡献使得信号肽在细菌分泌蛋白靶向中的重要性低于目前的假设。相反，它是他们的功能，作为变构激活剂的转位酶，使信号肽蛋白质分泌所必需的。信号肽和靶向序列作为变构激活剂的作用在蛋白质移位酶中可能是普遍的。
Extra-cytoplasmic polypeptides are usually synthesized as “preproteins” carrying aminoterminal, cleavable signal peptides and secreted across membranes by translocases. The main bacterial translocase comprises the SecYEG protein-conducting channel and the peripheral ATPase motor SecA. Most proteins destined for the periplasm and beyond are exported post-translationally by SecA. Preprotein targeting to SecA is thought to involve signal peptides and chaperones like SecB. Here we reveal that signal peptides have a novel role beyond targeting: they are essential allosteric activators of the translocase. Upon docking on their binding groove on SecA, signal peptides act in trans to drive three successive states: first, “triggering” that drives the translocase to a lower activation energy state; then “trapping” that engages non-native preprotein mature domains docked with high affinity on the secretion apparatus and, finally, “secretion” during which trapped mature domains undergo multiple turnovers of translocation in segments. A significant contribution by mature domains renders signal peptides less critical in bacterial secretory protein targeting than currently assumed. Rather, it is their function as allosteric activators of the translocase that renders signal peptides essential for protein secretion. A role for signal peptides and targeting sequences as allosteric activators may be universal in protein translocases.
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影响因子：
3.2
作者：
Smith, MA;Clemons, WM;Flower, AM
通讯作者：
Flower, AM
影响因子：
3.2
作者：
FLOWER, AM;DOEBELE, RC;SILHAVY, TJ
通讯作者：
SILHAVY, TJ
DOI：
10.1073/pnas.0600433103
发表时间：
2006-03-21
影响因子：
11.1
作者：
Stan, G;Brooks, BR;Thirumalai, D
通讯作者：
Thirumalai, D
影响因子：
64.5
作者：
HARTL, FU;LECKER, S;WICKNER, W
通讯作者：
WICKNER, W
影响因子：
16
作者：
Li, Weikai;Schulman, Sol;Rapoport, Tom A.
通讯作者：
Rapoport, Tom A.