Gary Daughdrill
Gary Daughdrill
Associate Professor, CMMB and Florida Center of Excellence for Biomolecular Identification and Targeted Therapeutics
Contact
Office:
Phone: 813/974-2503
Email:
Education
Ph.D. University of Oregon, 1997
Research
Research in my group is focused on determining realistic structural ensembles for intrinsically unstructured proteins. Over the last 20 years the number of protein structures solved by x-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy has increased dramatically, enhancing our understanding of protein function and the diseases associated with protein dysfunction. Another important outcome of the protein structure initiative is the discovery of numerous protein families that do not form compact rigid structures. These intrinsically unstructured proteins (IUPs) are common in nature and disrupting their function can also result in the onset of certain diseases.
In contrast to the nearly 50,000 atomic models for structured proteins, only a handful of realistic structural ensembles have been determined for IUPs. This makes it difficult to test at least two hypotheses:
(1) The structural ensembles of intrinsically unstructured proteins are specified by local interactions.
(2) Homologous proteins that are intrinsically unstructured will be structurally similar above a certain sequence identity.
To test these hypotheses, we are determining structural ensembles for a set of homologous proteins that are intrinsically unstructured. The work is being placed in an evolutionary context to permit an assessment of important structural features by virtue of their conservation and constitutes the first attempt to quantify the relationship between sequence identity and structural similarity for intrinsically unstructured proteins. One of the models chosen for this study is the tumor suppressor protein, p53, and structural ensembles will ultimately be used as templates for inhibitor design
If you choose to join my group you will be exposed to the latest techniques in protein expression and purification. Data used to determine structural ensembles is being collected at the new high field NMR facility in the Center for Biomolecular Identification and Targeted Therapeutics where 600 and 800 MHz spectrometers are available.
Recent Publications
David F. Lowry, Andrew Hausrath, and Gary W. Daughdrill (2008) A robust approach for analyzing a heterogeneous structural ensemble, Proteins 2008 Jun 5. [Epub ahead of print]
David F. Lowry, Amber Stancik, Ranjay Mann Shrestha, and Gary W. Daughdrill (2007) Modeling the accessible conformations of the intrinsically unstructured transactivation domain of p53, Proteins 71 (2) 587-598.
Pamela Vise, Bharat Baral, Amber Stancik, David F. Lowry and Gary W. Daughdrill (2007) Identifying long-range structure in the intrinsically unstructured transactivation domain of p53. Proteins 67 526-530.
Gary W. Daughdrill, Pranesh Narayanaswami, Sara Gilmore, Agniezka Belczyk, and Celeste J. Brown (2007) Dynamic behavior of an intrinsically unstructured linker domain is conserved in the face of negligible amino acid sequence conservation. J. Mol. Evol. 65 (3) 277-288.
Vise, P.D., Baral, B., Latos, A.J. and Daughdrill, G.W. (2005) NMR chemical shift and relaxation measurements provide evidence for the coupled folding and binding of the p53 transactivation domain. Nucleic Acids Research 33(7):2061-2077; doi:10.1093/nar/gki336.
Katie E. Olson, Pranesh Narayanaswami, Pamela D. Vise, David F. Lowry, Marc S. Wold, and Gary W. Daughdrill (2005) Secondary structure and dynamics of an intrinsically unstructured linker domain. J. Biomol. Struct. and Dyn. 23(2) 113-124.