---
_id: '12781'
abstract:
- lang: eng
  text: "Most energy in humans is produced in form of ATP by the mitochondrial respiratory
    chain consisting of several protein assemblies embedded into lipid membrane (complexes
    I-V). Complex I is the first and the largest enzyme of the respiratory chain which
    is essential for energy production. It couples the transfer of two electrons from
    NADH to ubiquinone with proton translocation across bacterial or inner mitochondrial
    membrane. The coupling mechanism between electron transfer and proton translocation
    is one of the biggest enigma in bioenergetics and structural biology. Even though
    the enzyme has been studied for decades, only recent technological advances in
    cryo-EM allowed its extensive structural investigation. \r\n\r\nComplex I from
    E.coli appears to be of special importance because it is a perfect model system
    with a rich mutant library, however the structure of the entire complex was unknown.
    In this thesis I have resolved structures of the minimal complex I version from
    E. coli in different states including reduced, inhibited, under reaction turnover
    and several others. Extensive structural analyses of these structures and comparison
    to structures from other species allowed to derive general features of conformational
    dynamics and propose a universal coupling mechanism. The mechanism is straightforward,
    robust and consistent with decades of experimental data available for complex
    I from different species. \r\n\r\nCyanobacterial NDH (cyanobacterial complex I)
    is a part of broad complex I superfamily and was studied as well in this thesis.
    It plays an important role in cyclic electron transfer (CET), during which electrons
    are cycled within PSI through ferredoxin and plastoquinone to generate proton
    gradient without NADPH production. Here, I solved structure of NDH and revealed
    additional state, which was not observed before. The novel “resting” state allowed
    to propose the mechanism of CET regulation. Moreover, conformational dynamics
    of NDH resembles one in complex I which suggest more broad universality of the
    proposed coupling mechanism.\r\n\r\nIn summary, results presented here helped
    to interpret decades of experimental data for complex I and contributed to fundamental
    mechanistic understanding of protein function.\r\n"
acknowledged_ssus:
- _id: EM-Fac
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Vladyslav
  full_name: Kravchuk, Vladyslav
  id: 4D62F2A6-F248-11E8-B48F-1D18A9856A87
  last_name: Kravchuk
citation:
  ama: Kravchuk V. Structural and mechanistic study of bacterial complex I and its
    cyanobacterial ortholog. 2023. doi:<a href="https://doi.org/10.15479/at:ista:12781">10.15479/at:ista:12781</a>
  apa: Kravchuk, V. (2023). <i>Structural and mechanistic study of bacterial complex
    I and its cyanobacterial ortholog</i>. Institute of Science and Technology Austria.
    <a href="https://doi.org/10.15479/at:ista:12781">https://doi.org/10.15479/at:ista:12781</a>
  chicago: Kravchuk, Vladyslav. “Structural and Mechanistic Study of Bacterial Complex
    I and Its Cyanobacterial Ortholog.” Institute of Science and Technology Austria,
    2023. <a href="https://doi.org/10.15479/at:ista:12781">https://doi.org/10.15479/at:ista:12781</a>.
  ieee: V. Kravchuk, “Structural and mechanistic study of bacterial complex I and
    its cyanobacterial ortholog,” Institute of Science and Technology Austria, 2023.
  ista: Kravchuk V. 2023. Structural and mechanistic study of bacterial complex I
    and its cyanobacterial ortholog. Institute of Science and Technology Austria.
  mla: Kravchuk, Vladyslav. <i>Structural and Mechanistic Study of Bacterial Complex
    I and Its Cyanobacterial Ortholog</i>. Institute of Science and Technology Austria,
    2023, doi:<a href="https://doi.org/10.15479/at:ista:12781">10.15479/at:ista:12781</a>.
  short: V. Kravchuk, Structural and Mechanistic Study of Bacterial Complex I and
    Its Cyanobacterial Ortholog, Institute of Science and Technology Austria, 2023.
date_created: 2023-03-31T12:24:42Z
date_published: 2023-03-23T00:00:00Z
date_updated: 2023-08-04T08:54:51Z
day: '23'
ddc:
- '570'
- '572'
degree_awarded: PhD
department:
- _id: GradSch
- _id: LeSa
doi: 10.15479/at:ista:12781
ec_funded: 1
file:
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  date_created: 2023-04-19T14:33:41Z
  date_updated: 2023-04-19T14:33:41Z
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file_date_updated: 2023-04-20T07:02:59Z
has_accepted_license: '1'
language:
- iso: eng
month: '03'
oa_version: Published Version
page: '127'
project:
- _id: 238A0A5A-32DE-11EA-91FC-C7463DDC885E
  grant_number: '25541'
  name: 'Structural characterization of E. coli complex I: an important mechanistic
    model'
- _id: 627abdeb-2b32-11ec-9570-ec31a97243d3
  call_identifier: H2020
  grant_number: '101020697'
  name: Structure and mechanism of respiratory chain molecular machines
publication_identifier:
  isbn:
  - 978-3-99078-029-9
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '12138'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Leonid A
  full_name: Sazanov, Leonid A
  id: 338D39FE-F248-11E8-B48F-1D18A9856A87
  last_name: Sazanov
  orcid: 0000-0002-0977-7989
title: Structural and mechanistic study of bacterial complex I and its cyanobacterial
  ortholog
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2023'
...