Bingdong Sha, Ph.D.
Professor, Department of Cell Biology
Areas of focus: Molecular Chaperones, Unfolded Protein Response, Mitochondrial Translocons
Visit Bingdong's Lab
Structural and functional studies of Molecular chaperones Hsp40 and Hsp70 - Hsp40 can bind non-native polypeptides to function as a molecular chaperone to suppress protein aggregation. Hsp40 can cooperate with Hsp70 to facilitate protein folding and assembly. The N-terminal J-domain of Hsp40 can stimulate the ATPase activity of Hsp70 while the C-terminal peptide-binding fragment of Hsp40 can deliver the non-native polypeptide to Hsp70 for subsequent protein folding. The mechanism of Hsp40 action as a molecular chaperone is unknown. X-ray protein crystallographic and biochemical studies are being carried out on Hsp40 to uncover how it interacts with the non-native polypeptides and transport them to Hsp70.
Structural and mechanistic studies of mitochondria translocons - Protein translocations across mitochondria membranes play critical roles in mitochondria biogenesis. The protein transports from the cell cytosol to the mitochondria matrix are carried out by the translocase of the outer membrane (TOM) complex and the translocase of the inner membrane (TIM) complex. The long-term goal of this project is to carry out structural studies on yeast TOM and TIM complexes to uncover the basic mechanisms by which these translocons facilitate the precursors across the outer and inner mitochondria membranes.
Structural studies for Unfolded Protein Response (UPR) related proteins - Endoplasmic reticulum (ER) stress can lead to protein overloading and protein misfolding within the ER lumen, which could induce the so-called unfolded protein responses (UPR). Several ER-resident stress sensor proteins such as IRE1, PERK and ATF-6 function to transduce the ER stress signals from ER lumen to trigger the UPR. In the normal conditions, the ER luminal domains of these sensor proteins bind the ER molecular chaperone Bip and these interactions inhibit the UPR signaling. In the stressed conditions, the dissociation of these sensor proteins from BiP may initiate the UPR due to the elevated misfolded protein concentration in ER. The UPR can lower the ER stress burden by regulating a number of transcription pathways. One major pathway is to reduce the ER protein influx and the second is to promote protein folding and degradation of the misfolded proteins within ER. Several ER protein chaperones are involved in UPR to facilitate protein dynamics. We are currently working on a number of UPR related protein structures to reveal the molecular mechanisms how UPR helps the cell to cope with ER stress.
Techniques used in the laboratory: Molecular biology, protein expression using prokaryotic and eukaryotic systems, protein biochemistry, protein purification and crystallization, protein crystallography, mass spectrometry and proteomics, protein interaction studies such as yeast two-hybrid, co-immunoprecipitation and pull-down assays, and protein biophysical studies such as laser scattering, and florescence and Isothermal titration calorimetry (ITC)
|The crystal structure of yeast Get3.
Get3 is an ATPase which facilitate
the biogenesis of the tail-anchored
Dr. Bingdong Sha is a Professor in the Department of Cell Biology. Dr. Sha received his B.S. degree at the University of Science and Technology of China in 1961 in Crystallography. He went on to receive his Ph.D. in Protein Crystallography at the Institute of Physics, Chinese Academy of Sciences in 1994. Dr. Sha completed his postdoctoral training in 1997 in the Center for Macromolecular Crystallography at UAB. He joined the UAB faculty in 1997.