Gongyi Zhang, Ph.D.
Assistant Professor of Immunology
National Jewish Medical and Research Center
1400 Jackson St., Room K405a
Denver, CO 80206
Tel: (303) 398-1715
Fax: (303) 398-1396
zhangg@njc.org
EDUCATION/EXPERIENCE
HONORS AND AWARDS
Research Interests
Structural
and functional analysis of TALL-1 and its cognate receptors. TALL-1 was
recently identified as a member of the tumor necrosis factor (TNF) ligand family,
that stimulates B cell proliferation and secretion of immunoglobulins. Overexpression
of TALL-1 in mice leads to autoimmune-like manifestations such as an increased
number of mature B cells, high levels of rheumatoid factors, circulating immune
complexes,
anti-DNA autoantibodies, and Ig deposition in the kidney.
The structure of the functional soluble TALL-1 (sTALL-1) has been determined at
3.0 Å resolution by X-ray crystallography. sTALL-1 forms a virus-like assembly
with 200 Å diameter in the crystals, containing 60 sTALL-1 monomers (see
Figure).
The cluster formation is mediated by a novel "flap"
region of the sTALL-1 monomer. The virus-like assembly was also detected in solution
using gel-filtration and electron microscopy.
Deletion of the "flap" region disrupted the ability
of the monomer to form the virus-like assembly. Although this mutant sTALL-1 retained
binding
capacity and affinity to its receptor, it did not function
to activate the transcription factor NF-kB. Finally, we found the virus-like cluster
of sTALL-1 exists in a nearly physiological condition.
We propose that this virus-like assembly of sTALL-1 is the
functional unit for TALL-1 in vivo. Structural determinations of sTALL-1 complex
with its cognate receptors are under progress. Characterization of the unique
signal transduction through TALL-1 is also our current focus.
Structural analysis of transcription factors of SarA family
from Staphylococcus aureus. The expression of virulence
determinants in Staphylococcus aureus is controlled by global regulatory loci
(e.g. sarA and agr). The sarA locus controls the expression of many virulence
genes including that of a-hemolysin (hla), protein A (spa) and fibronectin binding
protein A (fnbA). The major sarA regulatory molecule, SarA, is a 14.5 kD protein
(124 residues) that binds to the promoter region of target genes (e.g. agr, hla,
spa, and fnbA). From SarR (a homolog of SarA) structure, they represent a novel
atypical family member of 'Winged Helix' proteins. Our lab in collaborating with
Dr. Ambrose Cheung's lab at Dartmouth Medical School trys to understand the structural
basis of transcription regulation mechanism of SarA protein family. Our current
targets are SarA, SarR, SarS, and SarX, which is a homolog to MarR of E. coli.
Selected Publications
-
Yingfang Liu, Adhar Manna, Ambrose L. Cheung, and Gongyi Zhang. (2002)
A novel Transcription regulation revealed from the crystal structure of SarA protein
from S. aureus. (submitted).
-
Yingfang Liu, Lianggu Xu, Hong-Bing Shu, and Gongyi Zhnag. (2002).
Crystal structure of sTALL-1 reveals a virus-like structure of TNF family ligand.
Cell, 108, 383-394.
-
Yingfang Liu, Adhar Manna, Ronggui Li, Ambrose L. Cheung, Gongyi Zhang.
(2001). Crystal structure of the repressor protein SarR from S. aureus. Proc Natl
Acad Sci U S A. 98 (12): 6877-6882.
-
Gongyi Zhang, Elizabeth Campbell, Leonid Minakhin, Catherine Richter, Konstantin
Severinov, and Seth A. Darst. (1999). Crystal Structure of Thermus aquaticus core
RNA polymerase at 3.3 angstrom resolution. Cell, 98, 811-824. [Abstract]
-
Gongyi Zhang, Seth A. Darst. (1998).Structure of the E. coli RNA polymerase
alpha subunit N-terminal domain. Science, vol. 281; 262-266. [Abstract]
-
Gongyi Zhang, Yu Liu, Arnold E. Ruoho, and James H. Hurley. (1997).
Structure of the adenylyl cyclase catalytic core. Nature, vol. 386; 247-253.
[Absract]
-
Gongyi Zhang, Marcelo G. Kzanietz, Peter M. Blumberg, and James H.
Hurley. (1995). Crystal structure of the Cys2 activator-binding domain of protein
kinase C delta in complex with phorbol ester
Cell, vol. 81; 917-924. [Absract]
Bibliography
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