Mapping of the protein-binding interface between splicing factors SF3b155 and p14 of Trypanosoma cruzi.
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.
Avila
M Lara
ML
Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, INGEBI-CONICET, Vta. de obligado 2490, Buenos Aires, Argentina.
Bercovich
Natalia
N
Westergaard
Gastón
G
Levin
Mariano J
MJ
Vázquez
Martín P
MP
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010750:Phosphoproteins / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry*; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000737:chemistry*; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000737:chemistry*; D017381:Spliceosomes / Q000737:chemistry*; D014349:Trypanosoma cruzi / Q000737:chemistry
D010750:Phosphoproteins; D015800:Protozoan Proteins; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human; C437317:U2 small nuclear ribonucleoprotein p14