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Mitochondrial protein import.
Drašnarová, Zuzana ; Doležal, Pavel (advisor) ; Pyrih, Jan (referee)
Most of mitochondrial proteins are synthesized in the cytoplasm and after that transported to the outer or the inner membrane or to the intermembrane space and the mitochondrial matrix. All mitochondrial proteins cross the outer membrane via the TOM complex. From here different populations of proteins follow distinct transport routes: (i) β-barel proteins are assembled in the outer membrane with the help the SAM complex, (ii) after the passage through the TOM complex the intermembrane space proteins are bound by the MIA pathway, (iii) the mitochondrial carrier proteins of the inner mitochondrial membrane require the activity of the TIM22 complex and finally (iv) the matrix proteins as well as the small sub-population of the inner membrane proteins are transported via the TIM23 complex. Whereas the transport across the outer mitochondrial membrane does not require the additional energy, the transport across the inner membrane depends on ATP and/or the membrane potential. The transported proteins carry targeting sequences which are recognized by the outer membrane receptors. Key words: protein import, mitochondria, translocase, membrane, matrix, intermembrane space
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Cellular Protein Transport and Its Role in Patogenesis
Najdrová, Vladimíra ; Doležal, Pavel (advisor) ; Uzlíková, Magdalena (referee)
The main topic of this thesis are the protein secretion processes in several important human parasites - Toxoplasma gondii, Plasmodium falciparum, Trypanosoma cruzi, Leishmania spp. and Giardia intestinalis. Described here are the parasite's and the host proteins which participate in the pathogenic processes involving the protein secretion. As shown here, the protein secretion into the host environment is one of key tools serving the parasite to survive within and manipulate the host organism. Interestingly, different parasitic organisms use functionally and evolutionary distinct strategies to fulfill this aim. Key words secretory pathway, translocon, signal sequence, Toxoplasma gongii, Plasmodium falciparum, Trypanosoma cruzi, Leishmania spp., Giardia intestinalis
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Impact of the glycine-rich loop on the function of processing peptidases of the mitochondrial type
Kučera, Tomáš
A B S T R A C T The majority of the mitochondrial proteins is synthetized on the cytosolic ribosomes in the form of the protein precursors bearing mitochondrion-targeting signal presequences. Once the protein precursor has reached the mitochondrial matrix the signal presequence is no longer necessary and is cleaved off by heterodimeric mitochondrial processing peptidase (MPP; α/β). Although the crystal structure of MPP is available, the MPP mechanism of function is still matter of discussion. An all atomic, non-restrained molecular dynamics (MD) simulation in explicit water was used to study in detail the structural features of the highly conserved glycine-rich loop (GRL) of the regulatory α-subunit of the yeast MPP. Wild-type and GRL-deleted MPP structures were studied both in the presence and absence of a substrate in the peptidase active site. Targeted MD simulations were employed to study the mechanism of substrate translocation from the GRL to the peptidase active site. We demonstrate that the natural conformational flexibility of the GRL is crucial for the substrate translocation process from outside the enzyme towards the MPP active site. We show that the α-helical conformation of the substrate is important not only during its initial interaction with MPP (i.e. substrate recognition), but also later,...
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Impact of the glycine-rich loop on the function of processing peptidases of the mitochondrial type
Kučera, Tomáš ; Janata, Jiří (advisor) ; Bařinka, Cyril (referee) ; Ettrich, Rüdiger (referee)
The majority of the mitochondrial proteins is synthetized on the cytosolic ribosomes in the form of the protein precursors bearing mitochondrion-targeting signal presequences. Once the protein precursor has reached the mitochondrial matrix the signal presequence is no longer necessary and is cleaved off by heterodimeric mitochondrial processing peptidase (MPP; α/β). Although the crystal structure of MPP is available, the MPP mechanism of function is still matter of discussion. An all atomic, non-restrained molecular dynamics (MD) simulation in explicit water was used to study in detail the structural features of the highly conserved glycine-rich loop (GRL) of the regulatory α-subunit of the yeast MPP. Wild-type and GRL-deleted MPP structures were studied both in the presence and absence of a substrate in the peptidase active site. Targeted MD simulations were employed to study the mechanism of substrate translocation from the GRL to the peptidase active site. We demonstrate that the natural conformational flexibility of the GRL is crucial for the substrate translocation process from outside the enzyme towards the MPP active site. We show that the α-helical conformation of the substrate is important not only during its initial interaction with MPP (i.e. substrate recognition), but also later, at...
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Mitochondrial protein import.
Drašnarová, Zuzana ; Doležal, Pavel (advisor) ; Pyrih, Jan (referee)
Most of mitochondrial proteins are synthesized in the cytoplasm and after that transported to the outer or the inner membrane or to the intermembrane space and the mitochondrial matrix. All mitochondrial proteins cross the outer membrane via the TOM complex. From here different populations of proteins follow distinct transport routes: (i) β-barel proteins are assembled in the outer membrane with the help the SAM complex, (ii) after the passage through the TOM complex the intermembrane space proteins are bound by the MIA pathway, (iii) the mitochondrial carrier proteins of the inner mitochondrial membrane require the activity of the TIM22 complex and finally (iv) the matrix proteins as well as the small sub-population of the inner membrane proteins are transported via the TIM23 complex. Whereas the transport across the outer mitochondrial membrane does not require the additional energy, the transport across the inner membrane depends on ATP and/or the membrane potential. The transported proteins carry targeting sequences which are recognized by the outer membrane receptors. Key words: protein import, mitochondria, translocase, membrane, matrix, intermembrane space
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Impact of the glycine-rich loop on the function of processing peptidases of the mitochondrial type
Kučera, Tomáš
A B S T R A C T The majority of the mitochondrial proteins is synthetized on the cytosolic ribosomes in the form of the protein precursors bearing mitochondrion-targeting signal presequences. Once the protein precursor has reached the mitochondrial matrix the signal presequence is no longer necessary and is cleaved off by heterodimeric mitochondrial processing peptidase (MPP; α/β). Although the crystal structure of MPP is available, the MPP mechanism of function is still matter of discussion. An all atomic, non-restrained molecular dynamics (MD) simulation in explicit water was used to study in detail the structural features of the highly conserved glycine-rich loop (GRL) of the regulatory α-subunit of the yeast MPP. Wild-type and GRL-deleted MPP structures were studied both in the presence and absence of a substrate in the peptidase active site. Targeted MD simulations were employed to study the mechanism of substrate translocation from the GRL to the peptidase active site. We demonstrate that the natural conformational flexibility of the GRL is crucial for the substrate translocation process from outside the enzyme towards the MPP active site. We show that the α-helical conformation of the substrate is important not only during its initial interaction with MPP (i.e. substrate recognition), but also later,...
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Cellular Protein Transport and Its Role in Patogenesis
Najdrová, Vladimíra ; Doležal, Pavel (advisor) ; Uzlíková, Magdalena (referee)
The main topic of this thesis are the protein secretion processes in several important human parasites - Toxoplasma gondii, Plasmodium falciparum, Trypanosoma cruzi, Leishmania spp. and Giardia intestinalis. Described here are the parasite's and the host proteins which participate in the pathogenic processes involving the protein secretion. As shown here, the protein secretion into the host environment is one of key tools serving the parasite to survive within and manipulate the host organism. Interestingly, different parasitic organisms use functionally and evolutionary distinct strategies to fulfill this aim. Key words secretory pathway, translocon, signal sequence, Toxoplasma gongii, Plasmodium falciparum, Trypanosoma cruzi, Leishmania spp., Giardia intestinalis
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