Non-cryogenic structure and dynamics of HIV-1 integrase catalytic core domain by X-ray free-electron lasers

Jae Hyun Park; Ji Hye Yun; Yingchen Shi; Jeongmin Han; Xuanxuan Li; Zeyu Jin; Taehee Kim; Jaehyun Park; Sehan Park; Haiguang Liu; Weontae Lee

doi:10.3390/ijms20081943

Non-cryogenic structure and dynamics of HIV-1 integrase catalytic core domain by X-ray free-electron lasers

Jae Hyun Park, Ji Hye Yun, Yingchen Shi, Jeongmin Han, Xuanxuan Li, Zeyu Jin, Taehee Kim, Jaehyun Park, Sehan Park, Haiguang Liu, Weontae Lee

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Abstract

HIV-1 integrase (HIV-1 IN) is an enzyme produced by the HIV-1 virus that integrates genetic material of the virus into the DNA of infected human cells. HIV-1 IN acts as a key component of the Retroviral Pre-Integration Complex (PIC). Protein dynamics could play an important role during the catalysis of HIV-1 IN; however, this process has not yet been fully elucidated. X-ray free electron laser (XFEL) together with nuclear magnetic resonance (NMR) could provide information regarding the dynamics during this catalysis reaction. Here, we report the non-cryogenic crystal structure of HIV-1 IN catalytic core domain at 2.5 Å using microcrystals in XFELs. Compared to the cryogenic structure at 2.1 Å using conventional synchrotron crystallography, there was a good agreement between the two structures, except for a catalytic triad formed by Asp64, Asp116, and Glu152 (DDE) and the lens epithelium-derived growth factor binding sites. The helix III region of the 140-153 residues near the active site and the DDE triad show a higher dynamic profile in the non-cryogenic structure, which is comparable to dynamics data obtained from NMR spectroscopy in solution state.

Original language	English
Article number	1943
Journal	International journal of molecular sciences
Volume	20
Issue number	8
DOIs	https://doi.org/10.3390/ijms20081943
Publication status	Published - 2019 Apr 2

Bibliographical note

Funding Information:
Funding: This work was supported by NRF-2017R1A2B2008483, 2018K2A9A2A06024227 to W.L., and the Basic Science Research Program (NRF-2016R1A6A3A04010213 to J.-H.Y.) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education. The grants from National Natural Science Foundations (NSFC) to H. L. (No. 11575021, U1530401, U1430237) are acknowledged.

Funding Information:
Acknowledgments: We would like to express our gratitude to the staff scientists at the NCI Station of the Pohang Accelerator Laboratory X-ray Free Electron Laser, 5C and 7C beamline of the Pohang Accelerator Laboratory. This research was supported by a Tianhe-2JK Computing Time Award from the Beijing Computational Research Center (CSRC) and the experiments were performed at the NCI beamline of the PAL-XFEL (proposal no. 2018-2nd-NCI-016) funded by the Ministry of Science and ICT of Korea.

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

Catalysis
Molecular Biology
Spectroscopy
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry

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@article{f11ba3843b6f4d3fac937d4a7349be34,

title = "Non-cryogenic structure and dynamics of HIV-1 integrase catalytic core domain by X-ray free-electron lasers",

abstract = "HIV-1 integrase (HIV-1 IN) is an enzyme produced by the HIV-1 virus that integrates genetic material of the virus into the DNA of infected human cells. HIV-1 IN acts as a key component of the Retroviral Pre-Integration Complex (PIC). Protein dynamics could play an important role during the catalysis of HIV-1 IN; however, this process has not yet been fully elucidated. X-ray free electron laser (XFEL) together with nuclear magnetic resonance (NMR) could provide information regarding the dynamics during this catalysis reaction. Here, we report the non-cryogenic crystal structure of HIV-1 IN catalytic core domain at 2.5 {\AA} using microcrystals in XFELs. Compared to the cryogenic structure at 2.1 {\AA} using conventional synchrotron crystallography, there was a good agreement between the two structures, except for a catalytic triad formed by Asp64, Asp116, and Glu152 (DDE) and the lens epithelium-derived growth factor binding sites. The helix III region of the 140-153 residues near the active site and the DDE triad show a higher dynamic profile in the non-cryogenic structure, which is comparable to dynamics data obtained from NMR spectroscopy in solution state.",

author = "Park, {Jae Hyun} and Yun, {Ji Hye} and Yingchen Shi and Jeongmin Han and Xuanxuan Li and Zeyu Jin and Taehee Kim and Jaehyun Park and Sehan Park and Haiguang Liu and Weontae Lee",

note = "Funding Information: Funding: This work was supported by NRF-2017R1A2B2008483, 2018K2A9A2A06024227 to W.L., and the Basic Science Research Program (NRF-2016R1A6A3A04010213 to J.-H.Y.) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education. The grants from National Natural Science Foundations (NSFC) to H. L. (No. 11575021, U1530401, U1430237) are acknowledged. Funding Information: Acknowledgments: We would like to express our gratitude to the staff scientists at the NCI Station of the Pohang Accelerator Laboratory X-ray Free Electron Laser, 5C and 7C beamline of the Pohang Accelerator Laboratory. This research was supported by a Tianhe-2JK Computing Time Award from the Beijing Computational Research Center (CSRC) and the experiments were performed at the NCI beamline of the PAL-XFEL (proposal no. 2018-2nd-NCI-016) funded by the Ministry of Science and ICT of Korea. Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2019",

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doi = "10.3390/ijms20081943",

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AU - Park, Jae Hyun

AU - Yun, Ji Hye

AU - Shi, Yingchen

AU - Han, Jeongmin

AU - Li, Xuanxuan

AU - Jin, Zeyu

AU - Kim, Taehee

AU - Park, Jaehyun

AU - Park, Sehan

AU - Liu, Haiguang

AU - Lee, Weontae

N1 - Funding Information: Funding: This work was supported by NRF-2017R1A2B2008483, 2018K2A9A2A06024227 to W.L., and the Basic Science Research Program (NRF-2016R1A6A3A04010213 to J.-H.Y.) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education. The grants from National Natural Science Foundations (NSFC) to H. L. (No. 11575021, U1530401, U1430237) are acknowledged. Funding Information: Acknowledgments: We would like to express our gratitude to the staff scientists at the NCI Station of the Pohang Accelerator Laboratory X-ray Free Electron Laser, 5C and 7C beamline of the Pohang Accelerator Laboratory. This research was supported by a Tianhe-2JK Computing Time Award from the Beijing Computational Research Center (CSRC) and the experiments were performed at the NCI beamline of the PAL-XFEL (proposal no. 2018-2nd-NCI-016) funded by the Ministry of Science and ICT of Korea. Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2019/4/2

Y1 - 2019/4/2

N2 - HIV-1 integrase (HIV-1 IN) is an enzyme produced by the HIV-1 virus that integrates genetic material of the virus into the DNA of infected human cells. HIV-1 IN acts as a key component of the Retroviral Pre-Integration Complex (PIC). Protein dynamics could play an important role during the catalysis of HIV-1 IN; however, this process has not yet been fully elucidated. X-ray free electron laser (XFEL) together with nuclear magnetic resonance (NMR) could provide information regarding the dynamics during this catalysis reaction. Here, we report the non-cryogenic crystal structure of HIV-1 IN catalytic core domain at 2.5 Å using microcrystals in XFELs. Compared to the cryogenic structure at 2.1 Å using conventional synchrotron crystallography, there was a good agreement between the two structures, except for a catalytic triad formed by Asp64, Asp116, and Glu152 (DDE) and the lens epithelium-derived growth factor binding sites. The helix III region of the 140-153 residues near the active site and the DDE triad show a higher dynamic profile in the non-cryogenic structure, which is comparable to dynamics data obtained from NMR spectroscopy in solution state.

AB - HIV-1 integrase (HIV-1 IN) is an enzyme produced by the HIV-1 virus that integrates genetic material of the virus into the DNA of infected human cells. HIV-1 IN acts as a key component of the Retroviral Pre-Integration Complex (PIC). Protein dynamics could play an important role during the catalysis of HIV-1 IN; however, this process has not yet been fully elucidated. X-ray free electron laser (XFEL) together with nuclear magnetic resonance (NMR) could provide information regarding the dynamics during this catalysis reaction. Here, we report the non-cryogenic crystal structure of HIV-1 IN catalytic core domain at 2.5 Å using microcrystals in XFELs. Compared to the cryogenic structure at 2.1 Å using conventional synchrotron crystallography, there was a good agreement between the two structures, except for a catalytic triad formed by Asp64, Asp116, and Glu152 (DDE) and the lens epithelium-derived growth factor binding sites. The helix III region of the 140-153 residues near the active site and the DDE triad show a higher dynamic profile in the non-cryogenic structure, which is comparable to dynamics data obtained from NMR spectroscopy in solution state.

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Non-cryogenic structure and dynamics of HIV-1 integrase catalytic core domain by X-ray free-electron lasers

Abstract

Bibliographical note

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UN SDGs

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