Structure and function of Mycobacterium-specific components of F-ATP synthase subunits α and ε
The Mycobacterium tuberculosis (Mtb) F1FO-ATP synthase (α3:β3:γ:δ:ε:a:b:b’:c9) is an essential enzyme that supplies energy for both the aerobic growing and the hypoxic dormant stage of the mycobacterial life cycle. Employing the heterologous F-ATP synthase model system αchi3:β3:γ we showed previousl...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2020
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| Online Access: | https://hdl.handle.net/10356/139277 |
| _version_ | 1826110637344817152 |
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| author | Bogdanović, Nebojša Sundararaman, Lavanya Kamariah, Neelagandan Tyagi, Anu Bhushan, Shashi Ragunathan, Priya Shin, Joon Dick, Thomas Grüber, Gerhard |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Bogdanović, Nebojša Sundararaman, Lavanya Kamariah, Neelagandan Tyagi, Anu Bhushan, Shashi Ragunathan, Priya Shin, Joon Dick, Thomas Grüber, Gerhard |
| author_sort | Bogdanović, Nebojša |
| collection | NTU |
| description | The Mycobacterium tuberculosis (Mtb) F1FO-ATP synthase (α3:β3:γ:δ:ε:a:b:b’:c9) is an essential enzyme that supplies energy for both the aerobic growing and the hypoxic dormant stage of the mycobacterial life cycle. Employing the heterologous F-ATP synthase model system αchi3:β3:γ we showed previously, that transfer of the C-terminal domain (CTD) of Mtb subunit α (Mtα514-549) to a standard F-ATP synthase α subunit suppresses ATPase activity. Here we determined the 3D reconstruction from electron micrographs of the αchi3:β3:γ complex reconstituted with the Mtb subunit ε (Mtε), which has been shown to crosstalk with the CTD of Mtα. Together with the first solution shape of Mtb subunit α (Mtα), derived from solution X-ray scattering, the structural data visualize the extended C-terminal stretch of the mycobacterial subunit α. In addition, Mtε mutants MtεR62L, MtεE87A, Mtε6-121, and Mtε1-120, reconstituted with αchi3:β3:γ provided insight into their role in coupling and in trapping inhibiting MgADP. NMR solution studies of MtεE87A gave insights into how this residue contributes to stability and crosstalk between the N-terminal domain (NTD) and the CTD of Mtε. Analyses of the N-terminal mutant Mtε6-121 highlight the differences of the NTD of mycobacterial subunit ε to the well described Geobacillus stearothermophilus or Escherichia coli counterparts. These data are discussed in context of a crosstalk between the very N-terminal amino acids of Mtε and the loop region of one c subunit of the c-ring turbine for coupling of proton-translocation and ATP synthesis activity. |
| first_indexed | 2024-10-01T02:37:45Z |
| format | Journal Article |
| id | ntu-10356/139277 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:37:45Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1392772023-02-28T17:10:23Z Structure and function of Mycobacterium-specific components of F-ATP synthase subunits α and ε Bogdanović, Nebojša Sundararaman, Lavanya Kamariah, Neelagandan Tyagi, Anu Bhushan, Shashi Ragunathan, Priya Shin, Joon Dick, Thomas Grüber, Gerhard School of Biological Sciences NTU Institute of Structural Biology Science::Biological sciences::Biochemistry Science::Biological sciences::Molecular biology Mycobacterium F-ATP Synthase The Mycobacterium tuberculosis (Mtb) F1FO-ATP synthase (α3:β3:γ:δ:ε:a:b:b’:c9) is an essential enzyme that supplies energy for both the aerobic growing and the hypoxic dormant stage of the mycobacterial life cycle. Employing the heterologous F-ATP synthase model system αchi3:β3:γ we showed previously, that transfer of the C-terminal domain (CTD) of Mtb subunit α (Mtα514-549) to a standard F-ATP synthase α subunit suppresses ATPase activity. Here we determined the 3D reconstruction from electron micrographs of the αchi3:β3:γ complex reconstituted with the Mtb subunit ε (Mtε), which has been shown to crosstalk with the CTD of Mtα. Together with the first solution shape of Mtb subunit α (Mtα), derived from solution X-ray scattering, the structural data visualize the extended C-terminal stretch of the mycobacterial subunit α. In addition, Mtε mutants MtεR62L, MtεE87A, Mtε6-121, and Mtε1-120, reconstituted with αchi3:β3:γ provided insight into their role in coupling and in trapping inhibiting MgADP. NMR solution studies of MtεE87A gave insights into how this residue contributes to stability and crosstalk between the N-terminal domain (NTD) and the CTD of Mtε. Analyses of the N-terminal mutant Mtε6-121 highlight the differences of the NTD of mycobacterial subunit ε to the well described Geobacillus stearothermophilus or Escherichia coli counterparts. These data are discussed in context of a crosstalk between the very N-terminal amino acids of Mtε and the loop region of one c subunit of the c-ring turbine for coupling of proton-translocation and ATP synthesis activity. NRF (Natl Research Foundation, S’pore) Accepted version 2020-05-18T08:05:19Z 2020-05-18T08:05:19Z 2018 Journal Article Bogdanović, N., Sundararaman, L., Kamariah, N., Tyagi, A., Bhushan, S., Ragunathan, P., . . . Grüber, G. (2018). Structure and function of Mycobacterium-specific components of F-ATP synthase subunits α and ε. Journal of Structural Biology, 204(3), 420-434. doi:10.1016/j.jsb.2018.10.006 1047-8477 https://hdl.handle.net/10356/139277 10.1016/j.jsb.2018.10.006 30342092 2-s2.0-85055102909 3 204 420 434 en Journal of structural biology © 2018 Elsevier Inc. All rights reserved. This paper was published in Journal of structural biology and is made available with permission of Elsevier Inc. application/pdf |
| spellingShingle | Science::Biological sciences::Biochemistry Science::Biological sciences::Molecular biology Mycobacterium F-ATP Synthase Bogdanović, Nebojša Sundararaman, Lavanya Kamariah, Neelagandan Tyagi, Anu Bhushan, Shashi Ragunathan, Priya Shin, Joon Dick, Thomas Grüber, Gerhard Structure and function of Mycobacterium-specific components of F-ATP synthase subunits α and ε |
| title | Structure and function of Mycobacterium-specific components of F-ATP synthase subunits α and ε |
| title_full | Structure and function of Mycobacterium-specific components of F-ATP synthase subunits α and ε |
| title_fullStr | Structure and function of Mycobacterium-specific components of F-ATP synthase subunits α and ε |
| title_full_unstemmed | Structure and function of Mycobacterium-specific components of F-ATP synthase subunits α and ε |
| title_short | Structure and function of Mycobacterium-specific components of F-ATP synthase subunits α and ε |
| title_sort | structure and function of mycobacterium specific components of f atp synthase subunits α and ε |
| topic | Science::Biological sciences::Biochemistry Science::Biological sciences::Molecular biology Mycobacterium F-ATP Synthase |
| url | https://hdl.handle.net/10356/139277 |
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