Structural Biology/Biochemistry Seminar
Tuesday October 15, 2013
Kasha Laboratory, Room 112
11:15 AM
“Structure, function and evolution of intrinsically disordered proteins”

gdaughdrillDr. Gary Daughdrill

Associate Professor, University of South Florida
CMMB and Center for Drug Discovery and Innovation (CDDI)
Hosted by Dr. Huan-Xiang Zhou

http://biology.usf.edu/cmmb/faculty/gdaughdrill/

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