Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
PLoS One. 2011;6(9):e24547. doi: 10.1371/journal.pone.0024547. Epub 2011 Sep 8.
DegP, a member of the HtrA family of proteins, conducts critical bacterial protein quality control by both chaperone and proteolysis activities. The regulatory mechanisms controlling these two distinct activities, however, are unknown. DegP activation is known to involve a unique mechanism of allosteric binding, conformational changes and oligomer formation. We have uncovered a novel role for the residues at the PDZ1:protease interface in oligomer formation specifically for chaperone substrates of Chlamydia trachomatis HtrA (DegP homolog). We have demonstrated that CtHtrA proteolysis could be activated by allosteric binding and oligomer formation. The PDZ1 activator cleft was required for the activation and oligomer formation. However, unique to CtHtrA was the critical role for residues at the PDZ1:protease interface in oligomer formation when the activator was an in vitro chaperone substrate. Furthermore, a potential in vivo chaperone substrate, the major outer membrane protein (MOMP) from Chlamydia, was able to activate CtHtrA and induce oligomer formation. Therefore, we have revealed novel residues involved in the activation of CtHtrA which are likely to have important in vivo implications for outer membrane protein assembly.
DegP 是 HtrA 家族蛋白的成员，通过伴侣和蛋白水解活性来进行关键的细菌蛋白质量控制。然而，控制这两种不同活性的调节机制尚不清楚。DegP 的激活被认为涉及一种独特的变构结合、构象变化和寡聚体形成机制。我们发现了 PDZ1:蛋白酶界面残基在寡聚体形成中对于沙眼衣原体 HtrA（DegP 同源物）伴侣底物的一个新作用。我们已经证明 CtHtrA 的蛋白水解可以通过变构结合和寡聚体形成来激活。PDZ1 激活裂隙对于激活和寡聚体形成是必需的。然而，CtHtrA 的独特之处在于，在激活剂为体外伴侣底物时，PDZ1:蛋白酶界面残基在寡聚体形成中起着关键作用。此外，一种潜在的体内伴侣底物，即沙眼衣原体的主要外膜蛋白 (MOMP)，能够激活 CtHtrA 并诱导寡聚体形成。因此，我们揭示了参与 CtHtrA 激活的新残基，这些残基可能对外膜蛋白组装具有重要的体内意义。
