| Autor: |
Xu C; Advanced Materials Thrust, Function Hub, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, Guangdong 511400, China., Chu X; Advanced Materials Thrust, Function Hub, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, Guangdong 511400, China.; Guangzhou Municipal Key Laboratory of Materials Informatics, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, Guangdong 511400, China.; Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR 999077, China. |
| Jazyk: |
angličtina |
| Zdroj: |
Biochemistry [Biochemistry] 2024 Dec 17; Vol. 63 (24), pp. 3261-3272. Date of Electronic Publication: 2024 Nov 27. |
| DOI: |
10.1021/acs.biochem.4c00645 |
| Abstrakt: |
Engrailed homeodomain (EngHD), a highly charged transcription factor regulating over 200 genes, is a fast-folding protein. Recent studies have shown that the abundant charged residues in EngHD not only facilitate protein-DNA interactions but also influence the conformational disorder of its native structure. However, the mechanisms by which electrostatic interactions modulate the folding of EngHD remain unclear. Here, we employ a coarse-grained structure-based model that incorporates the salt-dependent Debye-Hückel model to investigate the (un)folding behavior of EngHD under various salt concentrations. Our findings demonstrate that increasing salt concentrations enhance both folding stability and cooperativity, while the folding barrier height remains relatively constant due to the distinct electrostatic effects on individual residues. By modulating the energetic balance between local and nonlocal interactions, we shift the folding of EngHD from a downhill process to a two-state process. Notably, we observe a nonmonotonic relationship between the strength of local interactions and residue-level coupling degree during (un)folding, likely attributed to the repulsive electrostatic interactions present in the native structure of EngHD. Additionally, we identify a critical turning point in the dependence of folding cooperativity on salt concentration, classified by the energetic balance of local and nonlocal interactions. Our results provide valuable insights into how electrostatic interactions influence the folding of EngHD, contributing to the theoretical framework for engineering highly charged proteins. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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