TCBG Seminar

Throwing a Curve at DNA: Structure and Function of Chromosomal HMG Proteins

Professor Mair Churchill
Department of Pharmacology
University of Colorado Health Sciences Center
Aurora, CO

Monday, April 4, 2005
3:00 pm (CT)
3269 Beckman Institute


Ubiquitous and abundant non-histone chromosomal proteins are essential for normal cellular function and are important in a wide variety of human diseases such as cancer, heart disease, deafness, aging, and diabetes. Such chromosomal proteins are called 'sequence-tolerant' or 'non-sequence-specific' DNA-binding proteins, because they have the ability to bind to different DNA sequences with comparable affinity. In particular, the High Mobility Group (HMG) chromosomal proteins are required for correct patterns of gene expression and DNA packaging in several organelles. They bind to DNA non-sequence- specifically, bend DNA dramatically, and recruit other proteins to the DNA to enhance transcription. However, the current understanding of their interactions with DNA and other proteins lags substantially behind that of sequence-specific counterparts. We have used HMG-D from Drosophila melanogaster as a model system for initial studies; it has the simplest structure of any HMG-box protein with only a single HMG-domain. It was amenable to a variety of biophysical and structural studies including NMR and X-ray crystallography. Structural studies of the HMG-D HMG domain-DNA complex reveal the nature of non-sequence-specific DNA binding, and calorimetric studies reveal the thermodynamic basis of non-sequence-specific DNA recognition. This work has greatly improved the understanding of the DNA binding properties of the HMG domain and non- sequence-specific DNA recognition in general, and lays the groundwork for understanding structural and mechanistic aspects of chromosomal HMGB function in higher order interactions with other proteins and DNA, as well as HMGB function in vivo.

Tea and coffee will be served in R3151 Beckman Institute at 2:15pm.

Main TCBG Seminars page