Bacillus licheniformis BlaR1 L3 loop is a zinc metalloprotease activated by self-proteolysis.

Bacillus licheniformis BlaR1 L3 loop is a zinc metalloprotease activated by self-proteolysis.
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DOI:
10.1371/journal.pone.0036400
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Joris B
Joris B
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Berzigotti S;Benlafya K;Sépulchre J;Amoroso A;Joris B

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在地衣芽孢杆菌749/I中,BlaP β-内酰胺酶由细胞外β-内酰胺抗生素的存在诱导。诱导机制的第一步是通过膜结合的青霉素受体BlaR 1检测抗生素,该受体由两个功能结构域组成:暴露在细胞外的羧基末端结构域,其充当青霉素传感器,以及锚定在细胞质膜上的氨基末端结构域,其充当转导-传递器。抗生素对BlaR 1传感器结构域的酰化产生分子内信号,该信号通过单点切割导致递质的L3细胞质环活化。L3激活的确切机制和由激活的递质发射的次级细胞质信号的性质仍然未知。然而,这两个事件似乎与中性锌金属肽酶的HEXXH锌结合基序的存在有关。通过不同的实验方法,我们证明了L3环与锌离子结合,属于谷锌素金属肽酶超家族,并通过自身蛋白水解被激活。
In Bacillus licheniformis 749/I, BlaP β-lactamase is induced by the presence of a β-lactam antibiotic outside the cell. The first step in the induction mechanism is the detection of the antibiotic by the membrane-bound penicillin receptor BlaR1 that is composed of two functional domains: a carboxy-terminal domain exposed outside the cell, which acts as a penicillin sensor, and an amino-terminal domain anchored to the cytoplasmic membrane, which works as a transducer-transmitter. The acylation of BlaR1 sensor domain by the antibiotic generates an intramolecular signal that leads to the activation of the L3 cytoplasmic loop of the transmitter by a single-point cleavage. The exact mechanism of L3 activation and the nature of the secondary cytoplasmic signal launched by the activated transmitter remain unknown. However, these two events seem to be linked to the presence of a HEXXH zinc binding motif of neutral zinc metallopeptidases. By different experimental approaches, we demonstrated that the L3 loop binds zinc ion, belongs to Gluzincin metallopeptidase superfamily and is activated by self-proteolysis.
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