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Structure Modeling of Toll-Like Receptors

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Innate DNA and RNA Recognition

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1169))

Abstract

Toll-like receptors (TLRs) recognize invasion of microbial pathogens and initiate innate immune responses that are essential for inhibiting pathogen dissemination and for the development of acquired immunity. To understand how these receptors work, it is crucial to investigate them from a structural perspective. High-throughput genome sequencing projects have led to the identification of more than 3,000 TLR sequences. However, only several structures of TLRs have been determined because structure determination by X-ray diffraction or nuclear magnetic resonance spectroscopy experiments remains difficult and time-consuming. Protein structure modeling methods are powerful tools for bridging the gap between sequence determination and structure determination. Due to different repeat numbers and distinct arrangements of leucine-rich repeats (LRRs) contained in TLR ectodomains, an automated homology modeling method often failed to predict a proper model. Here, we describe an LRR template assembly method for homology modeling of TLRs. This method was successfully validated through the comparison of a predicted model with the crystal structures, and showed better performance than other Protein structure modeling tools. The resulting models can be used to perform protein–ligand interaction studies or to design mutagenesis experiments, and hence to investigate TLR ligand-binding mechanisms.

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Acknowledgments

This work was supported by the Independent Innovation Foundation of Shandong University, China (No. 2011HW009) and the Promotive Research Fund for Excellent Young and Middle-aged Scientists of Shandong Province, China (No. BS2012SW010).

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Authors and Affiliations

  1. Cancer Research Center, School of Medicine, Shandong University, Jinan, 250012, China

    Jing Gong

  2. State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Jinan, 250100, China

    Tiandi Wei

Authors
  1. Jing Gong
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  2. Tiandi Wei
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Corresponding author

Correspondence to Tiandi Wei .

Editor information

Editors and Affiliations

  1. Ludwig Maximilians Universität München, Medizinische Klinik und Poliklinik IV, München, Germany

    Hans-Joachim Anders

  2. Helmholtz Zentrum MĂĽnchen German Researc, Institute for Diabetes and Regeneration, Munich, Germany

    Adriana Migliorini

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Gong, J., Wei, T. (2014). Structure Modeling of Toll-Like Receptors. In: Anders, HJ., Migliorini, A. (eds) Innate DNA and RNA Recognition. Methods in Molecular Biology, vol 1169. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0882-0_5

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  • DOI: https://doi.org/10.1007/978-1-4939-0882-0_5

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-0881-3

  • Online ISBN: 978-1-4939-0882-0

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