# positions[].organizations[].parent[].label
College of Agriculture and Life Sciences

# overview
The research in my lab focuses on elucidating the structural basis of innate immune responses towards microbial nucleic acids. The cGAS/STING pathway plays a central role in innate immunity toward bacterial and viral DNA. cGAS is activated by dsDNA and catalyzes the synthesis of a cyclic dinucleotide cGAMP, which binds to the adaptor STING that mediates the recruitment and activation of protein kinase TBK1 and transcription factor IRF-3. Activated IRF-3 translocates to the nucleus and induces the expression of type I interferons (IFN), an important family of antiviral cytokine. To elucidate the mechanism of cGAS activation, we determined the structures of cGAS in isolation and in complex with DNA. The cGAS/DNA complex structure reveals that cGAS interacts with DNA through two binding sites. Enzyme assays and IFN-? reporter assays of cGAS mutants demonstrate that interactions at both DNA binding sites are essential for cGAS activation. To investigate how cGAMP activates STING, we determined the structures of STING in isolation and in complex with cGAMP. These structures reveal that STING forms a V-shaped dimer and binds cGAMP at the dimer interface. We have also determined the structures of TBK1 in complex with two inhibitors, which show that TBK1 exhibits an I?B kinase fold with distinct domain arrangement. To elucidate the mechanism of IRF-3 recruitment by STING, we determined the structure of a phosphorylated STING peptide bound to IRF-3. To understand how phosphorylation activates IRF-3, we solved the structure of an IRF-3 phosphomimetic mutant bound to CBP, which reveals how phosphorylation induces the dimerization and activation of IRF-3.

# keywords[]
Intracellular Signaling Peptides And Proteins

# keywords[]
Intercellular Signaling Peptides And Proteins

# keywords[]
Nk Cell Lectin-like Receptor Subfamily K

# keywords[]
Nk Cell Lectin-like Receptor Subfamily K

# keywords[]
1.1 Normal Biological Development And Functioning

# keywords[]
Nk Cell Lectin-like Receptor Subfamily K

# keywords[]
Nk Cell Lectin-like Receptor Subfamily K

# educationAndTraining[].organization.label
Peking University - (Beijing, Beijing, China)

# educationAndTraining[].field
Structural Chemistry and Protein Crystallography

# publications[].label
Probing the metal specificity mechanism of superoxide dismutase from human pathogen Clostridium difficile.

# publications[].label
Mitochondrial dysfunction promotes alternative gasdermin D-mediated inflammatory cell death and susceptibility to infection

# publications[].label
The mechanism for heme to prevent A(1-40) aggregation and its cytotoxicity.

# publications[].label
Structure and function of the Zika virus full-length NS5 protein.

# publications[].label
Oligoadenylate-Synthetase-Family Protein OASL Inhibits Activity of the DNA Sensor cGAS during DNA Virus Infection to Limit Interferon Production.

# publications[].label
The structural basis of iron sensing by the human F-box protein FBXL5.

# publications[].label
The structure of a polyQ-anti-polyQ complex reveals binding according to a linear lattice model.

# publications[].label
The structural basis of 5' triphosphate double-stranded RNA recognition by RIG-I C-terminal domain.

# publications[].label
Erratum: The structure of a polyQanti-polyQ complex reveals binding according to a linear lattice model

# publications[].label
HLA-E allelic variants. Correlating differential expression, peptide affinities, crystal structures, and thermal stabilities.

# publications[].label
Structural and functional studies of the potent anti-HIV chemokine variant P2-RANTES.

# publications[].label
TRIM14 Is a Key Regulator of the Type I IFN Response during Mycobacterium tuberculosis Infection.

# publications[].publisher
The American Association of Immunologists

# publications[].label
Structure of STING bound to cyclic di-GMP reveals the mechanism of cyclic dinucleotide recognition by the immune system.

# publications[].label
Cd2+ as a Ca2+ surrogate in protein-membrane interactions: isostructural but not isofunctional.

# publications[].label
Preparation of Short RNA by In Vitro Transcription

# publications[].label
A conserved PLPLRT/SD motif of STING mediates the recruitment and activation of TBK1.

# publications[].label
The mechanism of double-stranded DNA sensing through the cGAS-STING pathway.

# publications[].label
Molecular Mechanisms of Tight Binding through Fuzzy Interactions.

# publications[].label
Regulation of de novo-initiated RNA synthesis in hepatitis C virus RNA-dependent RNA polymerase by intermolecular interactions.

# publications[].label
Structural basis of substrate selectivity of E. coli prolidase.

# publications[].label
Structural basis for concerted recruitment and activation of IRF-3 by innate immune adaptor proteins.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
The Structural Basis of IRF-3 Activation upon Phosphorylation.

# publications[].publisher
The American Association of Immunologists

# publications[].label
Structural and Biological Evaluations of a Non-Nucleoside STING Agonist Specific for Human STING A230 Variants.

# publications[].label
Viral DNA Binding to NLRC3, an Inhibitory Nucleic Acid Sensor, Unleashes STING, a Cyclic Dinucleotide Receptor that Activates Type I Interferon.

# publications[].label
The Molecular Mechanisms Underlying the Hijack of Host Proteins by the 1918 Spanish Influenza Virus.

# publications[].label
Cell type-specific function of TRAF2 and TRAF3 in regulating type I IFN induction.

# publications[].label
Crystallographic characterization of mouse AIM2 HIN-200 domain bound to a 15 bp and an 18 bp double-stranded DNA.

# publications[].publisher
International Union of Crystallography (IUCr)

# publications[].label
Structure and function of LGP2, a DEX(D/H) helicase that regulates the innate immunity response.

# publications[].label
Complex structure of the activating immunoreceptor NKG2D and its MHC class I-like ligand MICA.

# publications[].label
Hepatitis C Virus NS4B Can Suppress STING Accumulation To Evade Innate Immune Responses.

# publications[].label
Structural studies of allelic diversity of the MHC class I homolog MIC-B, a stress-inducible ligand for the activating immunoreceptor NKG2D.

# publications[].publisher
The American Association of Immunologists

# publications[].label
Preparation of short RNA by in vitro transcription.

# publications[].label
Crystal structure of RIG-I C-terminal domain bound to blunt-ended double-strand RNA without 5' triphosphate.

# publications[].label
NONO Detects the Nuclear HIV Capsid to Promote cGAS-Mediated Innate Immune Activation.

# publications[].label
Structural dynamics of receptor recognition and pH-induced dissociation of full-length Clostridioides difficile Toxin B.

# publications[].label
Molecular recognition of a host protein by NS1 of pandemic and seasonal influenza A viruses.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
The malectin-like receptor-like kinase LETUM1 modulates NLR protein SUMM2 activation via MEKK2 scaffolding.

# publications[].label
Single nucleotide polymorphisms of human STING can affect innate immune response to cyclic dinucleotides.

# publications[].label
Structural basis of double-stranded RNA recognition by the RIG-I like receptor MDA5.

# publications[].label
Probing the role of the bridging C509 between the [Fe4S4] cubane and the [Ni(p)Ni(d)] centre in the A-cluster of acetyl-coenzyme A synthase.

# publications[].label
TRIM14 is a key regulator of the type I interferon response during Mycobacterium tuberculosis infection

# publications[].label
A Quick Route to Multiple Highly Potent SARS-CoV-2 Main Protease Inhibitors*.

# publications[].label
Balancing the stability and the catalytic specificities of OP hydrolases with enhanced V-agent activities.

# publications[].label
Crystal structures of RAE-1beta and its complex with the activating immunoreceptor NKG2D.

# publications[].label
Cyclic GMP-AMP synthase is activated by double-stranded DNA-induced oligomerization.

# publications[].label
Correction for Yi et al., "Hepatitis C Virus NS4B Can Suppress STING Accumulation To Evade Innate Immune Responses".

# publications[].label
Crystal structure of the MHC class I homolog MIC-A, a gammadelta T cell ligand.

# publications[].label
Cyclic GMP-AMP Ameliorates Diet-induced Metabolic Dysregulation and Regulates Proinflammatory Responses Distinctly from STING Activation.

# publications[].label
RISC-interacting clearing 3'- 5' exoribonucleases (RICEs) degrade uridylated cleavage fragments to maintain functional RISC in Arabidopsis thaliana.

# publications[].label
The RIG-I-like receptor LGP2 recognizes the termini of double-stranded RNA.

# publications[].label
The ubiquitin ligase Peli1 negatively regulates T cell activation and prevents autoimmunity.

# publications[].label
Structural Basis of Protein Kinase C Regulation by the C-Terminal Tail.

# publications[].label
Quantitative Yeast Genetic Interaction Profiling of Bacterial Effector Proteins Uncovers a Role for the Human Retromer in Salmonella Infection.

# publications[].label
Tight Binding through Structural Disorder: Mechanism and Application

# publications[].label
Structural insights into the functions of TBK1 in innate antimicrobial immunity.

# publications[].label
Antitumor Activity of cGAMP via Stimulation of cGAS-cGAMP-STING-IRF3 Mediated Innate Immune Response.

# publications[].label
Insights into the mechanistic role of the [Fe4S4] cubane in the A-cluster {[Fe4S4]-(SR)-[NipNid]} of acetyl-coenzyme A synthase.

# publications[].label
New monoclonal anti-mouse DC-SIGN antibodies reactive with acetone-fixed cells.

# publications[].label
Agonist and antagonist recognition by RIG-I, a cytoplasmic innate immunity receptor.

# publications[].label
The deubiquitinase Otub1 controls the activation of CD8+ T cells and NK cells by regulating IL-15-mediated priming

# publications[].label
Pb2+ as modulator of protein-membrane interactions.

# publications[].label
SWI2/SNF2 ATPase CHR2 remodels pri-miRNAs via Serrate to impede miRNA production.

# publications[].label
The molecular basis of tight nuclear tethering and inactivation of cGAS.

# publications[].label
Interactions of human NKG2D with its ligands MICA, MICB, and homologs of the mouse RAE-1 protein family.

# researcherOn[].label
Develop General Methods for the Synthesis of Proteins with Posttranslational Lysine Modifications

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].awardedBy.preferredLabel
DHHS-NIH-National Institute of General Medical Science

# researcherOn[].label
The Secreted Effector SseC is a Key Regulator of Retrograde Transport During Salmonella Enterica Serovar Typhimurium Infection

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].awardedBy.preferredLabel
DHHS-NIH-National Institute of Allergy and Infectious Diseases

# researcherOn[].label
The Structural Basis of Viral RNA Sensing By the Rig-I Like Receptors

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].label
Tumor Suppression Through the cGAMP/STING Pathway

# researcherOn[].awardedBy.label
Cancer Prevention and Research Institute of Texas - (Austin, Texas, United States)

# researcherOn[].label
Hyperpolarization Assisted and Structure Based Screening of Protein-Ligand Interactions in Live Cells

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].awardedBy.preferredLabel
DHHS-NIH-National Institute of General Medical Science

# researcherOn[].label
The Molecular Basis of Viral DNA Sensing through the cGAS-STING Pathway

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].awardedBy.preferredLabel
DHHS-NIH-National Institute of Allergy and Infectious Diseases

# streetAddress
Texas A&M University; Biochemistry & Biophysics; 2128 TAMU

# schools[]
College of Agriculture and Life Sciences

# etdChairOf[].label
Kim, Yong-Ick (2009-05). The day/night switch of the circadian clock of synechococcus elongatus and hydrogen bonds of dna and rna. Doctoral Dissertation.

# etdChairOf[].label
Sung, Min Woo 1980- (2013-01). Mechanisms of Microbial DNA Sensing by the AIM2 Inflammasome and Structural Study of Polynucleotydyl Transferase1 (pnt1) from Arabidopsis Thaliana. Master's Thesis.

# etdChairOf[].label
Liu, Zhuyun (2009-05). Structural study of polyglutamine and molecular mechanism of toll-like receptor signaling. Master's Thesis.

# etdChairOf[].label
Watts, Tylan Aubrey (2013-05). Mechanism of MDA5 Recognition of Short RNA Ligands and Crystal Structure of PepQ. Master's Thesis.

# etdChairOf[].label
Kuo, Nai-Wei (2012-07). KaiC CII Ring Flexibility Governs the Rhythm of the Circadian Clock of Cyanobacteria. Doctoral Dissertation.

# etdChairOf[].label
Lu, Cheng (2012-10). Structural Basis of Viral RNA Recognition by RIG-I-Like Receptors. Doctoral Dissertation.