Computer aided protein engineering to enhance the thermo-stability of CXCR1- T4 lysozyme complex

Yang Wang, Jae Hyun Park, Cecylia Severin Lupala, Ji Hye Yun, Zeyu Jin, Lanqing Huang, Xuanxuan Li, Leihan Tang, Weon Tae Lee, Haiguang Liu

Research output: Contribution to journalArticle

Abstract

CXCR1, a member in G-protein coupled receptor (GPCR) family, binds to chemokine interleukin-8 (IL-8) specifically and transduces signals to mediate immune and inflammatory responses. Despite the importance of CXCR1, high-resolution structure determination is hindered by the challenges in crystallization. It has been shown that properly designed mutants with enhanced thermostability, together with fusion partner proteins, can be useful to form crystals for GPCR proteins. In this study, in silico protein design was carried out by using homology modeling and molecular dynamics simulations. To validate the computational modeling results, the thermostability of several mutants and the wild type were measured experimentally. Both computational results and experimental data suggest that the mutant L126W has a significant improvement in the thermostability. This study demonstrated that in silico design can guide protein engineering and potentially facilitate protein crystallography research.

Original languageEnglish
Article number5317
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

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Protein Engineering
Muramidase
G-Protein-Coupled Receptors
Computer Simulation
Proteins
Crystallography
Molecular Dynamics Simulation
Crystallization
Interleukin-8
Chemokines
Research

All Science Journal Classification (ASJC) codes

  • General

Cite this

Wang, Y., Park, J. H., Lupala, C. S., Yun, J. H., Jin, Z., Huang, L., ... Liu, H. (2019). Computer aided protein engineering to enhance the thermo-stability of CXCR1- T4 lysozyme complex. Scientific reports, 9(1), [5317]. https://doi.org/10.1038/s41598-019-41838-2
Wang, Yang ; Park, Jae Hyun ; Lupala, Cecylia Severin ; Yun, Ji Hye ; Jin, Zeyu ; Huang, Lanqing ; Li, Xuanxuan ; Tang, Leihan ; Lee, Weon Tae ; Liu, Haiguang. / Computer aided protein engineering to enhance the thermo-stability of CXCR1- T4 lysozyme complex. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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Wang, Y, Park, JH, Lupala, CS, Yun, JH, Jin, Z, Huang, L, Li, X, Tang, L, Lee, WT & Liu, H 2019, 'Computer aided protein engineering to enhance the thermo-stability of CXCR1- T4 lysozyme complex', Scientific reports, vol. 9, no. 1, 5317. https://doi.org/10.1038/s41598-019-41838-2

Computer aided protein engineering to enhance the thermo-stability of CXCR1- T4 lysozyme complex. / Wang, Yang; Park, Jae Hyun; Lupala, Cecylia Severin; Yun, Ji Hye; Jin, Zeyu; Huang, Lanqing; Li, Xuanxuan; Tang, Leihan; Lee, Weon Tae; Liu, Haiguang.

In: Scientific reports, Vol. 9, No. 1, 5317, 01.12.2019.

Research output: Contribution to journalArticle

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AU - Wang, Yang

AU - Park, Jae Hyun

AU - Lupala, Cecylia Severin

AU - Yun, Ji Hye

AU - Jin, Zeyu

AU - Huang, Lanqing

AU - Li, Xuanxuan

AU - Tang, Leihan

AU - Lee, Weon Tae

AU - Liu, Haiguang

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AB - CXCR1, a member in G-protein coupled receptor (GPCR) family, binds to chemokine interleukin-8 (IL-8) specifically and transduces signals to mediate immune and inflammatory responses. Despite the importance of CXCR1, high-resolution structure determination is hindered by the challenges in crystallization. It has been shown that properly designed mutants with enhanced thermostability, together with fusion partner proteins, can be useful to form crystals for GPCR proteins. In this study, in silico protein design was carried out by using homology modeling and molecular dynamics simulations. To validate the computational modeling results, the thermostability of several mutants and the wild type were measured experimentally. Both computational results and experimental data suggest that the mutant L126W has a significant improvement in the thermostability. This study demonstrated that in silico design can guide protein engineering and potentially facilitate protein crystallography research.

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