We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Surface plasmon resonance based analysis of the binding of LYAR protein to the rs368698783 (G>A) polymorphic Aγ-globin gene sequences mutated in β-thalassemia.
- Authors
Gemmo, Chiara; Breveglieri, Giulia; Marzaro, Giovanni; Lampronti, Ilaria; Cosenza, Lucia Carmela; Gasparello, Jessica; Zuccato, Cristina; Fabbri, Enrica; Borgatti, Monica; Chilin, Adriana; Finotti, Alessia; Gambari, Roberto
- Abstract
Recent studies have identified and characterized a novel putative transcriptional repressor site in a 5′ untranslated region of the Aγ-globin gene that interacts with the Ly-1 antibody reactive clone (LYAR) protein. LYAR binds the 5'-GGTTAT-3' site of the Aγ-globin gene, and this molecular interaction causes repression of gene transcription. In β-thalassemia patients, a polymorphism has been demonstrated (the rs368698783 G>A polymorphism) within the 5′-GGTTAT-3′ LYAR-binding site of the Aγ-globin gene. The major results gathered from surface plasmon resonance based biospecific interaction analysis (SPR-BIA) studies (using crude nuclear extracts, LYAR-enriched lysates, and recombinant LYAR) support the concept that the rs368698783 G>A polymorphism of the Aγ-globin gene attenuates the efficiency of LYAR binding to the LYAR-binding site. This conclusion was fully confirmed by a molecular docking analysis. This might lead to a very important difference in erythroid cells from β-thalassemia patients in respect to basal and induced levels of production of fetal hemoglobin. The novelty of the reported SPR-BIA method is that it allows the characterization and validation of the altered binding of a key nuclear factor (LYAR) to mutated LYAR-binding sites. These results, in addition to theoretical implications, should be considered of interest in applied pharmacology studies as a basis for the screening of drugs able to inhibit LYAR–DNA interactions. This might lead to the identification of molecules facilitating induced increase of γ-globin gene expression and fetal hemoglobin production in erythroid cells, which is associated with possible reduction of the clinical severity of the β-thalassemia phenotype.
- Subjects
FETAL hemoglobin; SURFACE plasmon resonance; CARRIER proteins; MOLECULAR interactions; GENE expression; BINDING sites
- Publication
Analytical & Bioanalytical Chemistry, 2019, Vol 411, Issue 29, p7699
- ISSN
1618-2642
- Publication type
Academic Journal
- DOI
10.1007/s00216-019-01987-9