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Comparative analysis of receptor binding by chicken and human interleukin-1β

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Abstract

Interleukin-1β (IL-1β) is an important cytokine in the immune system. Mammalian and avian IL-1βs share only 31-35% sequence identity, and the function of avian IL-1βs is less well understood by comparison. Although chicken and mammalian IL-1βs have similar tertiary structures, these ILs differ significantly with respect to receptor activation. Analysis of the structures and sequences of IL-1βs reveals that the major differences lie in loops. Modeling docking of chicken IL-1β to its receptor reveals that these variable loops are critical for receptor binding. Molecular dynamics simulations of the IL-1βs reveal significant changes in the dynamic range of motion upon receptor binding. Loops 3 and 9 of the unbound chicken IL-1β had greater fluctuations compared with the other loops. Upon binding, the flexibility of these loops, which directly contact the receptor, markedly decreases. Taken together, these results suggest that receptor binding leads to not only favorable enthalpy but also lower conformational entropy.

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Acknowledgments

The authors acknowledge the support of the National Science Council, Taiwan (NSC grant numbers NSC-96-2311-B-007-015-MY3). Portions of this research were carried out at the National Synchrotron Radiation Research Center, a national user facility supported by the National Science Council of Taiwan, ROC.

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  1. Institute of Bioinformatics and Structural Biology and College of Life Sciences, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu, Taiwan, 30013

    Chao-Sheng Cheng, Wen-Shiang Lu, I-Fan Tu, Ping-Chiang Lyu & Hsien-Sheng Yin

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  1. Chao-Sheng Cheng
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Correspondence to Hsien-Sheng Yin.

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Cheng, CS., Lu, WS., Tu, IF. et al. Comparative analysis of receptor binding by chicken and human interleukin-1β. J Mol Model 17, 1283–1294 (2011). https://doi.org/10.1007/s00894-010-0831-4

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