Modeling of PTF1‐J and PTF1‐L Heterotrimeric Transcription Factor Complexes (LB87)

• Published in: The FASEB journal 2014-04, Vol.28 (S1), p.n/a
• Main Authors: Pedigo, KK, Mainali, Rabina, Glispin, Christopher, Noble, Gabe, Petters, Garrett, Allmam, Casey, Agua, Alec Agua, Bauzaldua, Adrian, Crane, Ben, Aranoff, Max, Gonzales, Nicholas, Park, Christine, Chung, Elizabeth, Montoux, Amy, Flabiano, Meredith, Espinosa, Anika, Almazan, Selena, Kaye, Cassidy, Crowling, Anna, Chandler, Chandria, Allman, Julianna, Coats, Ward, MacDonald, Raymond
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.28.1_supplement.lb87

Students in Biomedical Research Studies at Hillcrest High School in Dallas, Texas participate in an ongoing research program at the University of Texas Southwestern Medical Center to study the structure and function of a transcription factor complex. Ptf1a is a transcription factor that is crucial to the development of the embryonic pancreas. Its functional form is in a trimeric complex composed of a heterodimer of E12/E47 and Ptf1a (basic helix‐loop‐helix transcription factors), and either Rbpj or Rbpjl (paralogs, also present in Notch signaling). The Rbpj form of the complex (PTF1‐J) is required for the early stage of pancreatic development. Subsequently, the Rbpjl‐form (PTF1‐L) is required for the formation of mature acinar cells of the exocrine pancreas. The Hillcrest SMART (Students Modeling A Research Topic) Team using 3D printing technology has generated models for the PTF1‐J and PTF1‐L transcription factor complexes. The models provide the orientation of the Ptf1a/E12 heterodimer relative to the Rbpj and Rbpjl proteins and characterizes interactions formed between Ptf1a (tryptophan 298) and a hydrophobic pocket present in the b‐trefoil domain of Rbpj or Rbpjl. Determination of the structures for the PTF1‐J and PTF1‐L complexes will help elucidate the structural determinants and the mechanism for the strong cooperative DNA binding of these complexes. Grant Funding Source: Supported by a grant from NIH‐SEPA and NIH‐CTSA.