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Structural and Biophysical Studies of the Pitx2 Homeodomain

Doerdelmann, Thomas
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1307443112

Abstract Details

2011, PhD, University of Cincinnati, Medicine: Molecular Genetics, Biochemistry, and Microbiology.
Transcription factors are modular proteins composed of distinct functional domains that are central to convert stored genetic information to functional protein. As such, they play fundamental roles in development and tissue maintenance throughout the eukaryotic life cycle. The homeodomain-containing transcription factor Pitx2 (pituitary homeobox protein 2) is present in many developing embryonic tissues, including the heart. Its homeodomain is responsible for the recognition and binding to target DNA sequences and thus constitutes a major functional unit in the Pitx2 protein. Mutations within the homeodomain have been directly linked to several developmental disorders including Axenfeld-Rieger Syndrome. Multidimensional Nuclear Magnetic Resonance techniques were employed to determine the solution structure of the native Pitx2 homeodomain and a R24H mutant that causes the autosomal dominantly inherited ring dermoid of the cornea syndrome. While the solution structures revealed that both isoforms possess the canonical homeodomain fold, additional biophysical studies unveiled differences in homeodomain stability, DNA-binding affinity, and transactivation activity.
Mark Rance, PhD (Committee Chair)
Jun Ma, PhD (Committee Member)
Gary Dean, PhD (Committee Member)
Andrew Herr, PhD (Committee Member)
Rhett Kovall, PhD (Committee Member)
211 p.
Biochemistry
Pitx2; Homeodomain; NMR; Protein Dynamics; Axenfeld-Rieger; Solution Structure

Recommended Citations

Citations

  • Doerdelmann, T. (2011). Structural and Biophysical Studies of the Pitx2 Homeodomain [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1307443112

    APA Style (7th edition)

  • Doerdelmann, Thomas. Structural and Biophysical Studies of the Pitx2 Homeodomain. 2011. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1307443112.

    MLA Style (8th edition)

  • Doerdelmann, Thomas. "Structural and Biophysical Studies of the Pitx2 Homeodomain." Doctoral dissertation, University of Cincinnati, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1307443112

    Chicago Manual of Style (17th edition)

ucin1307443112
305
© 2011, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.