Our research interests in one line include (1) protein structure-function analysis and (2) protein-protein interactions:
(1) The heat shock protein 70 (Hsp70) molecular chaperones are found ubiquitously in the cell and they have many important functions for cell survival; such as to prevent aggregation, fold nascent protein chains, aid translocation across cellular membranes, and assist in protein degradation. Hsp70s are constitutively expressed in all types of cells; also their expression can be enhanced by stress factors. Hsp70s are a conserved family of proteins that consist of an N-terminal ATPase domain and a C-terminal substrate-binding domain. ATP binding leads to reduced substrate-binding affinity for Hsp70s, and reciprocally, substrate-binding activates their ATPase rates. This interdomain communication is essential for Hsp70 chaperone function. Unfortunately, yet the lack of available structural information of full-length Hsp70s at different ligand-bound states limit our understanding for the allosteric signaling mechanism. With this project, we aim to understand the structural details of the signaling mechanism of DnaK, E. coli Hsp70, by the application of genetic engineering methods in combination with various biophysical and biochemical techniques. We also employ computational methods to our studies in order to better understand the molecular details of the signaling mechanism.
(2) Adaptor proteins play a key role in many physiological processes. We believe that understanding the molecular details of adaptor protein functions through the interactions with other partner proteins can open up new horizons for various therapy strategies. In our laboratory, we work on Bag-1 (Bcl-2 associated athono gene-1) adaptor protein which is the founding member of an anti-apoptotic Bag family. Bag-1 regulates a wide variety of cellular processes, including proliferation, survival, transcription, apoptosis, tumorigenesis and motility. To perform these functions Bag-1 has three functionally distinct isoforms that can interact with a diverse array of molecular targets such as Hsp70/Hsc70 molecular chaperones, components of the ubiquitylation/proteasome machinery, Bcl-2 apoptosis regulator, the Raf-1 kinase, nuclear hormone receptors and DNA. In human malignant cells, the expression of Bag-1 isoforms is frequently altered, and thus their expression profiles may serve as a powerful prognostic/predictive marker in carcinogenesis. Our goal in this project is to delineate the interacting partners of Bag-1 isoforms first in normal cells and later in malignant cells.
Another focus in the laboratory is to develop new strategies for microbial desulfurization of coals from Turkey and Bulgaria. Coal is a major source of energy for centuries. During coal combustion sulfur content of coal combines with oxygen to form sulfur oxides leading to hazardous environmental problems such as acid rains. Sulfur emissions can be controlled either removing the sulfur by pre-combustion or converting the sulfur dioxides to sulphate salts by post-combustion. It is believed that the best method to decrease the sulfur dioxide emission into atmosphere is to reduce the amount of coal before combustion. Sulfur content of various coals differs worldwide between 0.5% and 11% and the increasing amount of universal coal utilization necessitates limitation and ultimately elimination of the present sulfur in coal before combustion. The removal of sulfur from coal is a complicated process due to the presence of mainly different inorganic and organic forms of sulfur as pyrite, sulfate, inorganic sulfite, organic sulfur compounds and elemental sulfur, each requiring specific separation methods. These techniques include physical, chemical and biological processes. Removal of inorganic sulphur is easier than to that of organic sulfur compounds. The inability of physical and chemical methods to completely remove even the inorganic sulfur has led to the development of biodesulfurization processes which have significant advantages over the conventional technologies.Since high efficiency on the removal of certain impurities can be obtained with this method under milder reaction conditions. Our research mainly aims to optimize and improve the biological conditions of the microbial desulfurization process specifically for the removal of organic sulfur. In addition, our goal is to apply basic recombinant DNA technologies to enhance the efficiency of biodesulfurization reactions.