Mapping of the protein-binding interface between splicing factors SF3b155 and p14 of Trypanosoma cruzi

• Published in: Biochemical and biophysical research communications Vol. 364; no. 1; pp. 26 - 32
• Main Authors: Avila, M. Lara, Bercovich, Natalia, Westergaard, Gastón, Levin, Mariano J., Vázquez, Martín P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07-12-2007
• Subjects: Amino Acid Sequence; Animals; Drug targets; Humans; Molecular Sequence Data; Nuclear Magnetic Resonance, Biomolecular; Phosphoproteins - chemistry; Protein Binding; Protein interaction; Protein Structure, Tertiary; Protozoan Proteins - chemistry; Ribonucleoprotein, U2 Small Nuclear - chemistry; RNA Splicing Factors; RNA-Binding Proteins - chemistry; Spliceosomes - chemistry; Trans-splicing; Trypanosoma cruzi; Trypanosoma cruzi - chemistry; aa; NMR; Drug targets; Trans-splicing; 3AT; AY294609 for Tcp14; RRM; Protein interaction; RNA Recognition Motif
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2007.09.090

SF3b155 and p14 are essential components of spliceosome core that recognize the branch point adenosine, a critical step in splicing in eukaryotes. Trypanosomes are unusual since every transcribed gene is processed by
trans-splicing instead of
cis-splicing. Thus, the
trans-spliceosome emerges as an interesting anti-parasitic drug target since this process is not present in mammalian hosts. Here, we present the orthologues of these proteins in
Trypanosoma cruzi that interact strongly with each other. To define similarities and differences with the human pair, we performed a detailed alanine scan analysis that allowed us to identify the regions and the critical amino acids of
T. cruzi SF3b155 involved in interaction with p14. We demonstrate that the
T. cruzi SF3b155 interface is larger and contains more complex elements than its human counterpart. Additionally, our results provide the first insights into the core of the putative mRNA processing complex of trypanosomes.