Díaz-Casas, Adalberto

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    Prp40: A novel centrin-binding protein
    (2018) Díaz-Casas, Adalberto; Pastrana-Ríos, Belinda; College of Arts and Sciences - Sciences; Meléndez, Enrique; Ríos, Robert; Department of Chemistry; Plaza, María
    Pre-mRNA processing protein 40 (Prp40) is a modular protein that has an essential role in the initiation step of pre-mRNA splicing. In Homo sapiens, Prp40 has two putative homologs: Prp40 homolog A (HsPrp40A) and homolog B (HsPrp40B). This splicing factor comprises two WW domains and six tandem FF domains. In addition, Prp40 has two leucine-rich nuclear export signals, but little is known about the function of Prp40 in the export process. Centrin, a calcium-binding protein that is known to have a role in mRNA and protein export, is one of the 350 “eukaryotic signature proteins.” We identified a centrin-binding site that is located within the third FF (FF3) domain of HsPrp40A. This centrin-binding site is highly similar to the first nuclear export signal consensus sequence identified in yeast Prp40. We confirmed the interaction between a HsPrp40A synthetic peptide (HsPrp40Ap) and centrin, using isothermal titration calorimetry and two-dimensional infrared (2D IR) correlation spectroscopy. In addition, spectroscopic and thermodynamic studies carried out on HsPrp40A’s full FF3 domain provided new insights about the stability of this domain. Finally, we proceeded to study the molecular behavior of HsPrp40A’s FF3 domain under thermal stress, using differential scanning calorimetry, circular dichroism, and 2D IR correlation spectroscopies. The comprehensive body of evidence supports a novel centrin target with potential regulatory functions within the nucleus, the scientific implications being that the centrin-Prp40A complex has a functional role in pre-mRNA splicing.