Role of OSCP protein in bloodstream form and dyskinetoplastic Trypanosoma brucei

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F16%3A00488333" target="_blank" >RIV/60077344:_____/16:00488333 - isvavai.cz</a>

Result on the web

<a href="http://www.parazitologie.cz/protozoologie/Protodny2016/JPD_sbornik_2016.pdf" target="_blank" >http://www.parazitologie.cz/protozoologie/Protodny2016/JPD_sbornik_2016.pdf</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Role of OSCP protein in bloodstream form and dyskinetoplastic Trypanosoma brucei

Original language description

Mitochondrial (mt) ATP synthase is responsible of ATP generation in most eukaryotic cells. While the procyclic form (PF) of T. brucei uses the conventional function of the enzyme, the bloodstream form (BF) exploits the reversed ATP hydrolytic activity coupled to the proton translocation across the inner mt membrane in order to maintain the mt membrane potential. Despite ATP synthase overall structure and mechanism have remained conserved throughout evolution, composition of T. brucei's peripheral stalk, which docks F1 moiety to the membrane, differs remarkably, being OSCP the only conserved subunit thereof. In other species OSCP constitutes the only physical link of the peripheral stalk to F1-ATPase via an interaction with subunit. However, critical residues for the interaction are found neither in OSCP nor in subunit. Consequently, OSCP role in F1-ATPase immobilization remains hypothetical in T. brucei. OSCP is required for ATP synthase function in PF, as its silencing by RNAi resulted in an evident growth phenotype. In contrast, OSCP knock-down in BF or dyskinetoplastic (Dk) cell lines did not affect growth rate. ATP synthase of Dk cells cannot translocate protons due to the loss of the mt encoded proton pore subunit a. Nevertheless, ATP hydrolysis by F1-ATPase remains essential for by supplying ADP3-/ATP4-exchange across the mt membrane. OSCP double knockout in BF and in Dk cell lines will enable us to determine whether the F1-peripheral stalk interaction is OSCP-mediated, or involves other subunits, e.g. kinetoplastid-specific ATPaseTb2 (peripheral stalk) or p18 (F1 sector), and whether the interaction network is preserved in the reduced ATP synthase of Dk cells.n

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/LL1205" target="_blank" >LL1205: Exploration of the unique charakters od the Trypanosoma brucei FoF1 ATP synthase complex for future drug development against african sleeping sickness.</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

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