Premium
Modeling of the PTF1‐L/Foxa2 Transcription Factor Complex Controlling Pancreatic Development
Author(s) -
Coats Ward,
Pedigo K,
Noble G,
Glispin C,
Agha A,
Bazaldua A,
Aranoff M,
Bennett H,
Crowling A,
Gonzales N,
Montoux A,
Espinoza A,
Almazan S,
Allman C,
Kaye C,
Allman J,
Crane B,
Villegas A,
Broughton B,
McDonald Ray
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb56
Subject(s) - foxa2 , transcription factor , pancreas , forkhead transcription factors , microbiology and biotechnology , pax6 , chemistry , biology , endocrinology , gene , genetics
Students at Hillcrest High School in Dallas, Texas participate in a research program at the UT Southwestern Medical Center to study the structure of a transcription factor complex crucial to the embryonic development of the pancreas. Children without a functional Ptf1a transcription factor are born with a defective pancreas and are severely diabetic. The active form of Ptf1a is a trimeric complex composed of a common E‐box binding protein (e.g., E12/47), Ptf1a and Rbpj or Rbpjl. 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 acinar cells of the exocrine pancreas. Recruitment of Foxa2 to PTF1‐L bound sites of pancreatic genes occurs during the final maturation step of pancreas development. The Hillcrest SMART (Students Modeling A Research Topic) Team has manufactured a model for the PTF1‐L/Foxa2 transcription factor complex using 3D printing technology. The students using Pymol, Jmol and the known structures for Rbpj/Notch, MyoD, E12/E47 and Foxp2 generated the atomic coordinates for the model. The model provides the orientation of the Ptf1a/E12 heterodimer relative to Rbpjl and Foxa2 and characterizes interactions formed between Ptf1a and a hydrophobic pocket present in the beta‐trefoil domain of Rbpjl. Determination of the structure for the PTF1‐L/Foxa2 complex will help elucidate the structural determinants and the mechanism for the DNA binding of these complexes.