Inhibition of F-1-ATPase from Trypanosoma brucei by its regulatory protein inhibitor TbIF1

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F18%3A43897616" target="_blank" >RIV/60076658:12310/18:43897616 - isvavai.cz</a>

Alternative codes found

RIV/60077344:_____/18:00498618

Result on the web

<a href="https://febs.onlinelibrary.wiley.com/doi/epdf/10.1111/febs.14672" target="_blank" >https://febs.onlinelibrary.wiley.com/doi/epdf/10.1111/febs.14672</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/febs.14672" target="_blank" >10.1111/febs.14672</a>

Result language

angličtina

Original language name

Inhibition of F-1-ATPase from Trypanosoma brucei by its regulatory protein inhibitor TbIF1

Original language description

Hydrolysis of ATP by the mitochondrial F-ATPase is inhibited by a protein called IF1. In the parasitic flagellate, Trypanosoma brucei, this protein, known as TbIF1, is expressed exclusively in the procyclic stage, where the F-ATPase is synthesizing ATP. In the bloodstream stage, where TbIF1 is absent, the F-ATPase hydrolyzes ATP made by glycolysis and compensates for the absence of a proton pumping respiratory chain by translocating protons into the intermembrane space, thereby maintaining the essential mitochondrial membrane potential. We have defined regions and amino acid residues of TbIF1 that are required for its inhibitory activity by analyzing the binding of several modified recombinant inhibitors to F-1-ATPase isolated from the procyclic stage of T. brucei. Kinetic measurements revealed that the C-terminal portion of TbIF1 facilitates homodimerization, but it is not required for the inhibitory activity, similar to the bovine and yeast orthologs. However, in contrast to bovine IF1, the inhibitory capacity of the C-terminally truncated TbIF1 diminishes with decreasing pH, similar to full length TbIF1. This effect does not involve the dimerization of active dimers to form inactive tetramers. Over a wide pH range, the full length and C-terminally truncated TbIF1 form dimers and monomers, respectively. TbIF1 has no effect on bovine F-1-ATPase, and this difference in the mechanism of regulation of the F-ATPase between the host and the parasite could be exploited in the design of drugs to combat human and animal African trypanosomiases.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

FEBS Journal

ISSN

1742-464X

e-ISSN

—

Volume of the periodical

285

Issue of the periodical within the volume

23

Country of publishing house

GB - UNITED KINGDOM

Number of pages

11

Pages from-to

4413-4423

UT code for WoS article

000452404200007

EID of the result in the Scopus database

2-s2.0-85055177205