@article{bee9d11c276248e8b570b21e43b639a4,
title = "Structural basis underlying the synergism of NADase and SLO during group A Streptococcus infection",
abstract = "Group A Streptococcus (GAS) is a strict human pathogen possessing a unique pathogenic trait that utilizes the cooperative activity of NAD+-glycohydrolase (NADase) and Streptolysin O (SLO) to enhance its virulence. How NADase interacts with SLO to synergistically promote GAS cytotoxicity and intracellular survival is a long-standing question. Here, the structure and dynamic nature of the NADase/SLO complex are elucidated by X-ray crystallography and small-angle scattering, illustrating atomic details of the complex interface and functionally relevant conformations. Structure-guided studies reveal a salt-bridge interaction between NADase and SLO is important to cytotoxicity and resistance to phagocytic killing during GAS infection. Furthermore, the biological significance of the NADase/SLO complex in GAS virulence is demonstrated in a murine infection model. Overall, this work delivers the structure-functional relationship of the NADase/SLO complex and pinpoints the key interacting residues that are central to the coordinated actions of NADase and SLO in the pathogenesis of GAS infection.",
author = "Tsai, {Wei Jiun} and Lai, {Yi Hsin} and Shi, {Yong An} and Michal Hammel and Duff, {Anthony P.} and Whitten, {Andrew E.} and Wilde, {Karyn L.} and Wu, {Chun Ming} and Robert Knott and Jeng, {U. Ser} and Kang, {Chia Yu} and Hsu, {Chih Yu} and Wu, {Jian Li} and Tsai, {Pei Jane} and Chuan Chiang-Ni and Wu, {Jiunn Jong} and Lin, {Yee Shin} and Liu, {Ching Chuan} and Toshiya Senda and Shuying Wang",
note = "Funding Information: We thank the technical services provided by the “Synchrotron Radiation Protein Crystallography Facility of the National Core Facility Program for Biotechnology, Ministry of Science and Technology” and the “National Synchrotron Radiation Research Center”, a national user facility supported by the Ministry of Science and Technology, Taiwan. SAXS data were collected at the SIBYLS beamline at the Advanced Light Source (Berkeley, CA) which is supported by the National Institutes of Health (P30 GM124169), and the Integrated Diffraction Analysis Technologies program of the US Department of Energy Office of Biological and Environmental Research. The Advanced Light Source is a national user facility operated by Lawrence Berkeley National Laboratory on behalf of the US Department of Energy under contract DE-AC02-05CH11231, Office of Basic Energy Sciences. We also acknowledge ANSTO for access to the neutron scattering instrumentation via proposal DB9048 and the provision of deuterated material under proposals 9053 and 9058. The National Deuteration Facility is partly supported by the National Collaborative Research Infrastructure Strategy—an initiative of the Australian Government. This research was supported by grants (MOST 109-2320-B-006 -066 and MOST 110-2320-B-006 -023) to S.W. and fellowships from Ministry of Science and Technology and Xin Miao Education Foundation of Taiwan to W.J.T. We also thank Drs. Miki Senda, Meng-Chiao Ho, Ching-Hao Teng, Nadendla Eswarkumar, and Yu-Yuan Hsiao for their expertise and assistance throughout our study. Funding Information: We thank the technical services provided by the “Synchrotron Radiation Protein Crystallography Facility of the National Core Facility Program for Biotechnology, Ministry of Science and Technology” and the “National Synchrotron Radiation Research Center”, a national user facility supported by the Ministry of Science and Technology, Taiwan. SAXS data were collected at the SIBYLS beamline at the Advanced Light Source (Berkeley, CA) which is supported by the National Institutes of Health (P30 GM124169), and the Integrated Diffraction Analysis Technologies program of the US Department of Energy Office of Biological and Environmental Research. The Advanced Light Source is a national user facility operated by Lawrence Berkeley National Laboratory on behalf of the US Department of Energy under contract DE-AC02-05CH11231, Office of Basic Energy Sciences. We also acknowledge ANSTO for access to the neutron scattering instrumentation via proposal DB9048 and the provision of deuterated material under proposals 9053 and 9058. The National Deuteration Facility is partly supported by the National Collaborative Research Infrastructure Strategy—an initiative of the Australian Government. This research was supported by grants (MOST 109-2320-B-006 -066 and MOST 110-2320-B-006 -023) to S.W. and fellowships from Ministry of Science and Technology and Xin Miao Education Foundation of Taiwan to W.J.T. We also thank Drs. Miki Senda, Meng-Chiao Ho, Ching-Hao Teng, Nadendla Eswarkumar, and Yu-Yuan Hsiao for their expertise and assistance throughout our study. Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = jan,
day = "31",
doi = "10.1038/s42003-023-04502-0",
language = "English",
volume = "6",
journal = "Communications Biology",
issn = "2399-3642",
publisher = "Springer Nature",
number = "1",
}