7WDL

Fungal immunomodulatory protein FIP-nha

7WDL の概要

• エントリーDOI: 10.2210/pdb7wdl/pdb
• 分子名称: Fungal immunomodulatory protein (2 entities in total)
• 機能のキーワード: immunomodulatory, anti-tumor, tetramer, immune system
• 由来する生物種: Fusarium solani
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 55689.58

構造登録者

Liu, Y.,Bastiaan-Net, S.,Zhang, Y.,Hoppenbrouwers, T.,Xie, Y.,Wang, Y.,Wei, X.,Du, G.,Zhang, H.,Imam, K.M.S.U.,Wichers, H.J.,Li, Z. (登録日: 2021-12-22, 公開日: 2022-06-29, 最終更新日: 2023-11-29)

主引用文献

Liu, Y.,Bastiaan-Net, S.,Zhang, Y.,Hoppenbrouwers, T.,Xie, Y.,Wang, Y.,Wei, X.,Du, G.,Zhang, H.,Imam, K.M.D.S.U.,Wichers, H.,Li, Z.
Linking the thermostability of FIP-nha (Nectria haematococca) to its structural properties.
Int.J.Biol.Macromol., 213:555-564, 2022

PubMed Abstract: Fungal immunomodulatory proteins (FIPs) have been investigated for their use as potential natural derived anti-tumor molecules. However, the stability of FIPs is critical for their preparation and storage. In this study, the correlation between thermal stability and protein structural features of rFIP-nha, with significant anti-tumor activity, has been evaluated. For comprehensive analysis, FIP-nha and its homologues FIP-gmi, FIP-fve, and LZ-8 were all recombinantly expressed in E. coli. In solution, rFIP-nha and rFIP-gmi formed tetramers; rFIP-fve and rLZ-8 appeared as dimers. Their melting temperatures were 85.1 °C, 77.8 °C, 66.5 °C, and 64.4 °C, respectively. Accordingly, their cytotoxicity was also temperature dependent. To investigate the underlying mechanism of their thermostability, we solved the crystal structure of FIP-nha. Detailed structure analysis, molecular dynamic simulation and mutagenesis studies indicated that a higher thermostability was correlated to higher oligomerization states, larger interface area, and more interactions. The structure property studies indicate that Y12, D61 and Y108 were critical for oligomerization and high thermostability of rFIP-nha, but the dimeric and tetrameric states of rFIP-nha exert similar cytotoxicity on A549 cells. Taken together, these findings reveal that thermostability of FIPs was dependent on their oligomerization state, and correlated with their cytotoxicity.

PubMed: 35644318
DOI: 10.1016/j.ijbiomac.2022.05.136

実験手法

X-RAY DIFFRACTION (1.903 Å)