University of Nebraska Medical Center

Tahir Tahirov, PhD

Professor, UNMC Eppley Institute for Research in Cancer and Allied Diseases
Research focus: Structural biology/X-ray crystallography


Research Interests

Human genome contains all the information necessary to maintain and continue the life, and two basic processes are most important for that. One is a transcription of genetic information which leads to synthesis of proteins and another one is a replication and maintenance of the genomic information itself. Both of these processes are very complicated, involving large macromolecular machines and networks of highly coordinated events requiring protein-protein and protein-nucleic acid interactions. The disruptions in these events often lead to cancers and a variety of other diseases and disorders. The long term goal of our laboratory is to reveal the structural basis of the mechanisms covering the key stages in the expression and duplication/repair of genes and to learn how the disease-related mutations in proteins disrupt these key processes. Our research is based primarily on X-ray crystallography - the powerful method which provides the most precise three-dimensional structure of biological macromolecules. 

To learn about the details of available projects, students and researchers are welcome to visit the Tahirov lab.

Completed projects:

Structural analyses of DNA recognition by the Runx1 and its allosteric control by CBFβ

The core binding factor (CBF) heterodimeric transcription factors comprised of Runx and CBFβ subunits are essential for differentiation of hematopoietic and bone cells, and their mutation is intimately related to the development of acute leukemias and cleidocranial dysplasia. We solved the crystal structures of the Runx1(Runt domain)-CBFβ(core domain)-C/EBPβ(bZip)-DNA, Runx1(Runt)- C/EBPβ(bZip)-DNA, and Runx1(Runt)-DNA complexes. The hydrogen bonding network formed among Runx1 and CBFβ, and Runx1 and DNA revealed the allosteric regulation mechanism of Runx1-DNA binding by CBFβ. The point mutations of Runx1 related to acute leukemias and Runx2 point mutations related to cleidocranial dysplasia were also mapped and their effect on DNA binding and heterodimerization with CBFβ has been discussed. Cell 104:755-767

Mechanism of c-Myb-C/EBPβ cooperation from separated sites on a promoter 

c-Myb, but not avian myeloblastosis virus (AMV) v-Myb, cooperates with C/EBPβ to regulate transcription of myeloid-specific genes. To assess the structural basis for that difference, we determined the crystal structures of complexes comprised of the c-Myb or AMV v-Myb DNA-binding domain (DBD), the C/EBPβ DBD, and a promoter DNA fragment. Within the c-Myb complex, a DNA-bound C/EBPβ interacts with R2 of c-Myb bound to a different DNA fragment; point mutations in v-Myb R2 eliminate such interaction within the v-Myb complex. GST pull-down assays, luciferase trans-activation assays, and atomic force microscopy confirmed that the interaction of c-Myb and C/EBPβ observed in crystal mimics their long range interaction on the promoter, which is accompanied by intervening DNA looping. Cell 108:57-70

Structure and Function of Thermus thermophilus Δ1-pyrroline-5-carboxylate dehydrogenase (P5CDh)

P5CDh plays an important role in the metabolic pathway from proline to glutamate. It irreversibly catalyzes the oxidation of glutamate-γ-semialdehyde, the product of the non-enzymatic hydrolysis of Δ1-pyrroline-5-carboxylate, into glutamate with the reduction of NAD+ into NADH. We have confirmed the P5CDh activity of the Thermus thermophilus protein TT0033 (TtP5CDh), and determined the crystal structure of the enzyme in the ligand-free form at 1.4 Å resolution. To investigate the structural basis of TtP5CDh function, the TtP5CDh structures with NAD+, with NADH, and with its product glutamate were determined. The solved structures suggest an overall view of the P5CDh catalytic mechanism and provide insights into the P5CDh deficiencies in the case of the human type II hyperprolinemia. J Mol Biol 362:490-501