IdentificaÃÃo e mapeamento de domÃnios de ligaÃÃo de homÃlogos do fator eIF4G de iniciaÃÃo da traduÃÃo de Leishmania major

AUTOR(ES)

Christian Robson de Souza Reis

DATA DE PUBLICAÇÃO

2009

RESUMO

The trypanosomatids are characterized for unusual molecular process as pos-transcriptional control of gene expression, through mRNA degradation and translation control. In the majority of the eukaryotes, translation initiation starts with the binding of the translation initiation complex eIF4F (formed by the subunits eIF4A, eIF4E and eIF4G) to the monomethylated cap present on the 5âend of the mRNAs allowing itâs recognition by the ribosome and others eIFs participants. The eIF4F activity is enhanced by the poly(A) binding protein (PABP), which acts through a direct interaction with eIF4G. Several homologues to the eIF4F subunits and PABP have been previously identified in trypanosomatids, as five homologues of eIF4G (EIF4G1-5) and multiple homologues to the others subunits (EIF4E1-4, EIF4AI-III and PABP1-2) and their functions have been investigated in Leishmania major and Trypanosoma brucei. As a part of this work, we showed that both LmEIF4G3 and LmEIF4G4 interact with LmEIF4AI, however mutations in LNK residues of these proteins abolish their interactions with LmEIF4AI. The LmEIF4G3 and LmEIF4G4 also respectively bind to LmEIF4E4 and LmEIF4E3 homologues and different residues were associated to these interactions. Substitution of FSL residues in LmEIF4G3 abrogates your interaction with the LmEIF4E4 and IL residues mutagenesis in LmEIF4G4 abolishes itâs interaction to the LmEIF4E3. Additionally, we showed that LmEIF4G3 and LmEIF4G4 binding to LmPABP1 and we also suggest distinct functions for TbEIF4AI and TbEIF4AIII in both procyclic and bloodstream forms of T. brucei. To sum up, our findings indicate the major complexity of translation initiation in trypanosomatids and probably it is regulated by at least two different eIF4F complexes.

ASSUNTO(S)

eif4f eif4f translation initiation leishmania major â traduÃÃo â genÃtica tripanossomatÃdeos trypanosomatids genetica

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