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Structural Modeling of the C‐terminal Domain of Ptf1a Bound to Mammalian Rbpj and Rbpjl
Author(s) -
Osborn Nicholas,
Mayberry Brett,
Fein Zachary,
MacDonald Raymond,
Coats Ward
Publication year - 2011
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.25.1_supplement.lb168
Subject(s) - transcription factor , binding site , transcription (linguistics) , notch signaling pathway , microbiology and biotechnology , chemistry , biology , genetics , gene , linguistics , philosophy
As a means to introduce biomedical research to high school students, the MacDonald laboratory at UT Southwestern Medical Center at Dallas has engaged students from Hillcrest High School in an ongoing research program to study the structure and function of a mammalian transcription factor complex. Ptf1a is a transcription factor that is crucial to the development of the embryonic pancreas. Ptf1a acts within the context of a trimeric complex composed of three DNA‐binding subunits: a common E‐box binding protein (E12/47, HEB, or TCF12), Ptf1a, and either Rbpj or Rbpjl. The Rbpj form of the complex (PTF1‐J) is required for the early stage of pancreatic development, whereas the Rbpjl form (PTF1‐L) is necessary for acinar development. Tryptophan 298 located in a conserved sequence (C2) near the C terminus of Ptf1a is required for the recruitment of Rbpj into the PTF1‐J complex. The binding of the RAM domain of Notch‐IC to a hydrophobic pocket in Rbpj involves residues in a conserved hydrophobic, tryptophan, hydrophobic, proline motif that is also present in the C2 sequence of Ptf1a suggesting a similar hydrophobic pocket binding interaction for tryptophan 298. We have modeled the C2 sequence of Ptf1a onto the crystal structure of the RAM domain of Notch‐IC bound to Rbpj to characterize this binding interaction and to generate structure models for the complex of C2 with mammalian Rbpj and Rbpjl.