Chaperones Skp and SurA dynamically expand unfolded OmpX and synergistically disassemble oligomeric aggregates.
Chaperones Skp and SurA dynamically expand unfolded OmpX and synergistically disassemble oligomeric aggregates.
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DOI：
10.1073/pnas.2118919119
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发表时间：
2022-03-01
影响因子：
11.1
通讯作者：
Schlierf M
中科院分区：
文献类型：
--
作者：
Chamachi N;Hartmann A;Ma MQ;Svirina A;Krainer G;Schlierf M
外膜蛋白（OMP）对细菌的生存至关重要。两种分子伴侣17千道尔顿蛋白（Skp）和生存因子A（SurA）通过保持未折叠的OMP蛋白可溶于周质中而在OMP成熟中起关键作用。然而，它们的功能并不完全清楚。在这里，我们在与展开的OmpX交互时建立了两个伴侣所采用的结构和能量特征之间的联系。我们发现，扩展，伴随着快速的多肽链重构，防止未折叠的OmpX错误折叠和聚集。此外，分子伴侣与未折叠的OmpX的相互作用是精确校准的，允许在腺苷三磷酸耗尽的周质中分子伴侣与OMP的微调关联。我们进一步发现，Skp和SurA作为解聚剂一起起作用，并且能够分解寡聚OMP聚集体，揭示了这种周质伴侣系统的显著功能。周质伴侣17千道尔顿蛋白（Skp）和生存因子A（SurA）是外膜蛋白（OMP）生物合成的重要参与者。它们防止未折叠的OMP在其通过周质空间期间错误折叠，并在细胞应激条件下帮助OMP聚集体的分解。然而，相互作用机制，结构动力学和能量学之间的重要联系，支持Skp和SurA协会与外膜蛋白在很大程度上仍然没有得到解决。在这里，使用单分子荧光光谱，我们解剖的构象动力学和热力学的Skp和SurA结合未折叠的OmpX，并探讨其解聚酶的活动。我们发现，这两个分子伴侣扩展未折叠的OmpX明显，并诱导微秒链重构的客户端OMP结构。我们进一步揭示，Skp和SurA结合其基板在一个微调的热力学过程中，通过熵补偿。最后，我们观察到两种分子伴侣在寡聚OmpX聚集体的解聚中的协同活性。我们的研究结果提供了一个亲密的看法到Skp和SurA的多方面功能和微调之间的平衡构象的灵活性和潜在的能量在OMP生物发生过程中协助伴侣作用。
Outer membrane proteins (OMPs) are crucial for the survival of bacteria. The two chaperones 17-kilodalton protein (Skp) and survival factor A (SurA) play key roles in OMP maturation by keeping unfolded OMP proteins soluble in the periplasm. However, their functionalities are incompletely understood. Here, we establish connections between structural and energetic features employed by the two chaperones when interacting with unfolded OmpX. We find that expansion, accompanied with fast polypeptide chain reconfiguration, prevents unfolded OmpX from misfolding and aggregating. Moreover, chaperone interaction with unfolded OmpX is thermodynamically calibrated, allowing for a fine-tuned association of chaperones with OMPs in the adenosine triphosphate-depleted periplasm. We further discovered that Skp and SurA act together as disaggregases and are able to disassemble oligomeric OMP aggregates, revealing remarkable functionalities of this periplasmic chaperone system. Periplasmic chaperones 17-kilodalton protein (Skp) and survival factor A (SurA) are essential players in outer membrane protein (OMP) biogenesis. They prevent unfolded OMPs from misfolding during their passage through the periplasmic space and aid in the disassembly of OMP aggregates under cellular stress conditions. However, functionally important links between interaction mechanisms, structural dynamics, and energetics that underpin both Skp and SurA associations with OMPs have remained largely unresolved. Here, using single-molecule fluorescence spectroscopy, we dissect the conformational dynamics and thermodynamics of Skp and SurA binding to unfolded OmpX and explore their disaggregase activities. We show that both chaperones expand unfolded OmpX distinctly and induce microsecond chain reconfigurations in the client OMP structure. We further reveal that Skp and SurA bind their substrate in a fine-tuned thermodynamic process via enthalpy–entropy compensation. Finally, we observed synergistic activity of both chaperones in the disaggregation of oligomeric OmpX aggregates. Our findings provide an intimate view into the multifaceted functionalities of Skp and SurA and the fine-tuned balance between conformational flexibility and underlying energetics in aiding chaperone action during OMP biogenesis.
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DOI：
10.1039/c0cp01911a
发表时间：
2011-02-07
期刊：
Physical chemistry chemical physics : PCCP
影响因子：
--
作者：
Hoffmann A;Nettels D;Clark J;Borgia A;Radford SE;Clarke J;Schuler B
通讯作者：
Schuler B
影响因子：
5.6
作者：
Jefferson RE;Min D;Corin K;Wang JY;Bowie JU
通讯作者：
Bowie JU
DOI：
10.1073/pnas.1601002113
发表时间：
2016-08-16
影响因子：
11.1
作者：
Costello, Shawn M.;Plummer, Ashlee M.;Fleming, Karen G.
通讯作者：
Fleming, Karen G.
影响因子：
3.4
作者：
Denoncin, Katleen;Schwalm, Jaclyn;Vertommen, Didier;Silhavy, Thomas J.;Collet, Jean-Francois
通讯作者：
Collet, Jean-Francois
影响因子：
7.4
作者：
Hartmann, Andreas;Krainer, Georg;Schlierf, Michael
通讯作者：
Schlierf, Michael