Department of Chemistry, University of British Columbia, Vancouver, BC, V6T 1Z1, Canada.
State Key Laboratory of Precision Measuring Technology and Instruments, School of Precision Instrument and Optoelectronics Engineering, Tianjin University, 300072, Tianjin, P. R. China.
Nat Commun. 2022 May 19;13(1):2784. doi: 10.1038/s41467-022-30448-8.
The RTX (repeats-in-toxin) domain of the bacterial toxin adenylate cyclase (CyaA) contains five RTX blocks (RTX-i to RTX-v) and its folding is essential for CyaA's functions. It was shown that the C-terminal capping structure of RTX-v is critical for the whole RTX to fold. However, it is unknown how the folding signal transmits within the RTX domain. Here we use optical tweezers to investigate the interplay between the folding of RTX-iv and RTX-v. Our results show that RTX-iv alone is disordered, but folds into a Ca-loaded-β-roll structure in the presence of a folded RTX-v. Folding trajectories of RTX-iv-v reveal that the folding of RTX-iv is strictly conditional upon the folding of RTX-v, suggesting that the folding of RTX-iv is templated by RTX-v. This templating effect allows RTX-iv to fold rapidly, and provides significant mutual stabilization. Our study reveals a possible mechanism for transmitting the folding signal within the RTX domain.
RTX（重复毒素）结构域的细菌毒素腺苷酸环化酶（CyaA）包含五个 RTX 结构域（RTX-i 到 RTX-v），其折叠对于 CyaA 的功能至关重要。已经表明，RTX-v 的 C 末端加帽结构对于整个 RTX 的折叠至关重要。然而，目前尚不清楚折叠信号如何在 RTX 结构域内传递。在这里，我们使用光学镊子研究了 RTX-iv 和 RTX-v 之间的折叠相互作用。我们的结果表明，RTX-iv 单独是无定形的，但在折叠的 RTX-v 的存在下折叠成一个 Ca 负载的β-滚结构。RTX-iv-v 的折叠轨迹表明，RTX-iv 的折叠严格依赖于 RTX-v 的折叠，这表明 RTX-iv 的折叠是由 RTX-v 模板化的。这种模板效应允许 RTX-iv 快速折叠，并提供显著的相互稳定。我们的研究揭示了 RTX 结构域内传递折叠信号的可能机制。
