Secretion of atypical protein substrates by the ESAT-6 secretion system of Staphylococcus aureus.

Secretion of atypical protein substrates by the ESAT-6 secretion system of Staphylococcus aureus.
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DOI:
10.1111/mmi.12395
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发表时间:
2013-11
影响因子:
3.6
通讯作者:
Missiakas D
Missiakas D
中科院分区:
生物学2区
文献类型:
--
作者:
Anderson M;Aly KA;Chen YH;Missiakas D

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金黄色葡萄球菌编码ESAT-6分泌系统(ESS)。EsxA和EsxB通过ESS途径分泌,具有结核分枝杆菌VII型分泌系统(T7SS) ESAT-6和CFP-10的序列特征。与ESAT-6和CFP-10不同,EsxA和EsxB不相互作用。相反,EsxB与一种新的底物EsxD结合,EsxA与自身或EsxC (EsaC)二聚体。与EsxA和EsxB不同,EsxC和EsxD不具有明显的WXG100蛋白序列特征,也不具有PE/PPE和Esp蛋白家族的序列特征,它们都属于分枝杆菌T7SS的最重要的EsxAB家族。EsxD携带C端基序YxxxD/E,该基序已被提出用于分枝杆菌分泌T7底物。在这里,我们发现该基序的缺失(而不是氨基酸替换)阻止了EsxA和EsxC的分泌,但不能阻止EsxB或EsxD的分泌。这与esxA、esxB、esxC或esxD的基因失活不同,后者会导致所有四种底物的分泌丧失。因此,可以通过删除EsxD的最后六个氨基酸来解耦底物分泌。EsxC和EsxD与典型WXG100蛋白的物理关联表明,这些蛋白属于EsxAB家族。
Staphylococcus aureus encodes the specialized ESAT-6 Secretion System (ESS). EsxA and EsxB are secreted by the ESS pathway, and share sequence features of ESAT-6 and CFP-10 of the Type VII Secretion System (T7SS) of Mycobacterium tuberculosis. Unlike ESAT-6 and CFP-10, EsxA and EsxB do not interact. Instead, EsxB associates with a novel substrate, EsxD, and EsxA dimerizes with itself or EsxC (EsaC). Unlike EsxA and EsxB, EsxC and EsxD do not share obvious sequence features of WXG100 proteins nor PE/PPE and Esp families of proteins, all of which belong to the pfam EsxAB clan of mycobacterial T7SS. EsxD carries the C terminal motif YxxxD/E that has been proposed to target T7 substrates for secretion in mycobacteria. Here, we find that deletion, but not amino acid substitutions, in this motif prevent secretion of EsxA and EsxC but not EsxB or EsxD. This is unlike the genetic inactivation of esxA, esxB, esxC or esxD that leads to loss of secretion of all four substrates. Thus, substrate secretion can be uncoupled by deleting the last six amino acids of EsxD. The physical association of EsxC and EsxD with canonical WXG100 proteins suggests that these proteins belong to the EsxAB clan.
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