Located in the inner mitochondrial membrane, uncoupling proteins (UCPs) dissipate the proton electrochemical gradient causing reduction in the rate of ATP synthesis. Five human UCP homologues have been identified in different tissues to date; UCP1 is the only member of the UCP family with a well-characterized thermogenic role in brown adipose tissue.
Other members of the human UCP family are distributed at various tissues and their physiological roles are not well defined. With no high-resolution structure available, the structures of the prototypical UCP1 and other UCPs have been assumed to resemble the crystal structure of the ADP/ATP carrier (AAC).
Currently, we are interested in learning the structure and function of these proteins. In order to achieve this goal, we have developed an in-vitro system mimicking the inner mitochondrial membrane to track the transport activity and conformation of UCPs. Different molecular biology and biophysical techniques are currently used to study the structure and function of these proteins.
The long-range goal of this research is apply this in-vitro system to generate fundamental information on UCPs’ physiological roles in different tissues.
Publications on UCPs from our lab (list of publications)
Hoang T, Smith MD, Jelokhani-Niaraki M. 2012. Toward understanding the ion transport activity of neuronal uncoupling proteins UCP2, UCP4, and UCP5. Biochemistry 51(19), 4004-4014.
Ivanova MV, Hoang T, McSorley FR, Krnac G, Smith MD, Jelokhani-Niaraki M. 2010. A comparative study on conformation and ligand binding of the neuronal uncoupling proteins. Biochemistry 49(3), 512-521.
Jelokhani-Niaraki M, Ivanova MV, McIntyre BL, Newman CL, McSorley FR, Young EK, Smith MD, Jelokhani-Niaraki M. 2008. A CD study of uncoupling protein-1 and its transmembrane and matrix-loop domains. Biochem J 411, 593-603.
Yamaguchi H, Jelokhani-Niaraki M, Kodama H. 2004. Second transmembrane domain of human uncoupling protein 2 is essential for its ion channel formation. FEBS Lett 577, 299-304.