Institute of Medical Biochemistry (IBqM), National Center of Nuclear Magnetic Resonance, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
National Center of Nuclear Magnetic Resonance (CNRMN), National Center for Structural Biology and Bioimaging (CENABIO), Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Biomol NMR Assign. 2024 Dec;18(2):257-262. doi: 10.1007/s12104-024-10197-z. Epub 2024 Oct 14.
The Rho GTPase (Ras homolog GTPases) system is a crucial signal transducer that regulates various cellular processes, including cell cycle and migration, genetic transcription, and apoptosis. In this study, we investigated the unfolded state of the first FF domain (FF1) of P190A RhoGAP, which features four tandem FF domains. For signal transduction, FF1 is phosphorylated at tyrosine 308 (Y308), which is buried in the hydrophobic core and is inaccessible to kinases in the folded domain. It was proposed, therefore, that the phosphorylation occurs in a transiently populated unfolded state of FF1. To probe the folding pathway of the RhoGAP FF1 domain, here we have performed a nearly complete backbone resonance assignments of a putative partially unfolded state of FF1 in 5 M urea and its fully unfolded state in 8 M urea.
Rho GTPase（Ras 同源 GTPases）系统是一种关键的信号转导因子，调节各种细胞过程，包括细胞周期和迁移、基因转录和细胞凋亡。在这项研究中，我们研究了具有四个串联 FF 结构域的 P190A RhoGAP 第一个 FF 结构域（FF1）的展开状态。对于信号转导，FF1 在酪氨酸 308（Y308）处发生磷酸化，该残基埋藏在疏水区，在折叠结构域中激酶无法接近。因此，提出磷酸化发生在 FF1 的瞬时展开状态。为了探究 RhoGAP FF1 结构域的折叠途径，我们在 5 M 脲中进行了 FF1 部分展开状态的几乎完整的主链共振分配，在 8 M 脲中进行了其完全展开状态的主链共振分配。
