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Faculty Detail     Name BINGDONG SHA   Campus Address MCLM 364 Zip 0005 Phone 205-934-6446 E-mail bdsha@uab.edu Other websites

Faculty Appointment(s) Appointment Type Department Division Rank Primary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Professor Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor

Graduate Biomedical Sciences Affiliations Biochemistry and Structural Biology  Cancer Biology  Cell, Molecular, & Developmental Biology  Cellular and Molecular Biology Program  Medical Scientist Training Program

Society Memberships Organization Name Position Held Org Link American Association for the Advancement of Science (AAAS)  Member    American Crystallography Association   Member

Research/Clinical Interest Title Structural and functional studies of proteins involved in protein folding and translocations Description 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.

Selected Publications  Publication PUBMEDID Li, J. and Sha, B.D. (2002) "Crystal structure of E. coli Hsp100 ClpB nucleotide-binding domain 1 (NBD1) and mechanistic studies on ClpB ATPase activity." J. Mol. Biol. 318, 1127-1137.  12623019  Li, J. and Sha, B.D. (2002) "Cloning, expression, purification and preliminary X-ray crystallographic studies of E. coli Hsp100 nucleotide binding domain 2 (NBD2)". Acta Crystallogr. D58, 1030-1031.  12037306  Qian, X., Hou, W., Li, Z. and Sha, B.D. (2002) "Direct interactions between molecular chaperones Hsp70 and Hsp40: yeast Hsp70 Ssa1 binds the extreme C-terminal region of yeast Hsp40 Sis1." Biochem. J., 361, 27-34.  11743879  Wu, Y. and Sha, B.D. (2006) “Crystal structure of yeast mitochondria translocon member Tom70p”, Nature Struct. Mol. Biol. 13, 589-93.    Josyula, R., Jin, Z., Fu, Z. and Sha, B.D. (2006) “Crystal structure of yeast peripheral mitochondrial membrane protein Tim44p C-terminal domain”, J. Mol. Bio. 359, 798-804.    Li, J., Wu, Y., Qian, X. and Sha, B.D. (2006) “The crystal structure of the yeast Hsp40 Sis1 complexed with Hsp70 Ssa1.” Biochem J, 398, 353-360.    Wu, Y., Li., J., Jin, Z., Fu, Z. and Sha, B.D. (2005) “The crystal structure of the C-terminal fragment of yeast Hsp40 Ydj1 reveals novel dimerization motif for Hsp40.” J. Mol. Biol., 346, 1005-11.    Li, J., and Sha, B.D. (2005) “Structure-based mutagenesis studies of the peptide substrate binding fragment of type I heat-shock protein 40.” Biochem. J. 386, 453-60.    Li, J., Qian, X., and Sha, B.D. (2003) “The crystal structure of the yeast Hsp40 Ydj1 complexed with its peptide substrate”. Structure (Camb). 11(12):1475-83.    Li, J. and Sha, B.D. (2002) "Crystal structure of E. coli ClpB N-terminal domain." Structure, 11, 1.

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