A5044967018- Cell Adhesion Molecules Research
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Lipid Membrane Structure and Behavior
- Bone and Dental Protein Studies
- Platelet Disorders and Treatments
- Glycosylation and Glycoproteins Research
- Macrophage Migration Inhibitory Factor
- Complement system in diseases
- Toxin Mechanisms and Immunotoxins
- Force Microscopy Techniques and Applications
- TGF-β signaling in diseases
- Immune Response and Inflammation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Drug Transport and Resistance Mechanisms
- Synthesis and Catalytic Reactions
- Advanced Biosensing Techniques and Applications
- Cholesterol and Lipid Metabolism
- dental development and anomalies
- Malaria Research and Control
- Galectins and Cancer Biology
- Adenosine and Purinergic Signaling
- Neurogenetic and Muscular Disorders Research
- Gold and Silver Nanoparticles Synthesis and Applications
Tianjin University
2015-2024
Harvard University
2007-2015
Boston Children's Hospital
2009-2015
Children's Hospital 1
2012
Howard Hughes Medical Institute
2012
Harvard Stem Cell Institute
2008
Ajou University
2007
Beth Israel Deaconess Medical Center
2007
University of Virginia
2000-2005
University of Virginia Health System
2003
The mechanisms by which signals are transmitted across the plasma membrane to regulate signaling largely unknown for receptors with single-pass transmembrane domains such as epidermal growth factor receptor (EGFR).A crystal structure of extracellular domain EGFR dimerized (EGF) reveals extended, rod-like IV and a small, hydrophobic interface compatible flexibility.The disulfide cross-linking suggest that 7-residue linker between is flexible.Disulfide shows EGF stimulates only moderate...
Bone morphogenetic proteins (BMPs) belong to the TGF-β family, whose 33 members regulate multiple aspects of morphogenesis. family are secreted as procomplexes containing a small growth factor dimer associated with two larger prodomains. As isolated procomplexes, some latent, whereas most active; what determines these differences is unknown. Here, studies on pro-BMP structures and binding receptors lead insights into mechanisms that latency in functions their highly divergent The observed...
Circumsporozoite (CS) protein is the major surface component of Plasmodium falciparum sporozoites and essential for host cell invasion. A vaccine containing tandem repeats, region III, thrombospondin type-I repeat (TSR) CS efficacious in phase III trials but gives only a 35% reduction severe malaria first year postimmunization. We solved crystal structures showing that TSR fold into single unit, an “αTSR” domain. The αTSR domain possesses hydrophobic pocket core, missing domains. binds...
The lymphocyte homing receptor integrin α4β7 is unusual for its ability to mediate both rolling and firm adhesion. α4β1 are targeted by therapeutics approved multiple sclerosis Crohn’s disease. Here, we show electron microscopy crystallography how two therapeutic Fabs, a small molecule (RO0505376), mucosal adhesion molecule-1 (MAdCAM-1) bind α4β7. A long binding groove at the α4–β7 interface immunoglobulin superfamily domains differs in shape from pockets that Arg-Gly-Asp motifs. RO0505376...
We study a mechanism by which dimerization of the EGF receptor (EGFR) cytoplasmic domain is transmitted to ectodomain. Therapeutic and other small molecule antagonists kinase that stabilize its active conformation, but not those an inactive ectodomain dimerization. Inhibitor-induced requires asymmetric interface associated with activation. inhibitors stimulate formation identical dimer interfaces in EGFR transmembrane domain, as shown disulfide cross-linking. Disulfide cross-linking at IV...
Cellular signaling mediated by the epidermal growth factor receptor (EGFR or ErbB) family of tyrosine kinases plays an important role in regulating normal and oncogenic cellular physiology. While structures isolated EGFR extracellular domains intracellular protein kinase have suggested mechanisms for factor-mediated dimerization allosteric domain activation, understanding how transmembrane juxtamembrane contribute to requires structural studies on intact molecules. In this report,...
Many questions about the significance of structural features integrin α(V)β(3) with respect to its mechanism activation remain. We have determined and re-refined crystal structures ectodomain linked C-terminal coiled coils (α(V)β(3)-AB) four transmembrane (TM) residues in each subunit (α(V)β(3)-1TM), respectively. The α(V) β(3) subunits eight extracellular domains, respectively, are bent at knees between headpiece lower legs, has closed, low-affinity conformation. differ occupancy three...
Integrin α(X)β(2) functions as complement receptor for iC3b and mediates recognition phagocytosis of pathogens. We used negative-stain EM to examine the interaction with iC3b. class averages in complex define binding sites on both integrin contains C3c thioester domain moieties linked by a long flexible linker. The site is key ring moiety, at interface between MG3 MG4 domains. Similar complexes are seen fragment. binds through α(X) αI domain, face known bear metal ion-dependent adhesion...
Abstract An unprecedented epidemic of Zika virus (ZIKV) infection had spread to South and Central America. ZIKV was recently confirmed by CDC (the Centers for Disease Control Prevention) cause neonatal microcephaly, which posed a significant public health emergency international concern. No specific vaccines or drugs are currently available fight infection. nonstructural protein 1 (NS1) plays an essential role in viral replication immune evasion. We determined the crystal structure NS1...
The Ig superfamily (IgSF) intercellular adhesion molecule-1 (ICAM-1) equilibrates between monomeric and dimeric forms on the cell surface, dimerization enhances adhesion. A crystal structure of ICAM-1 IgSF domains (D) 3–5 revealed a unique interface in which D4s two protomers fuse through edge β-strands to form single super β-sandwich domain. Here, we describe at 2.7-Å resolution D3–D5, stabilized by monomer-specific Fab CA7. CA7 binds D5 region that is buried distal from site D4. In...
GM2-activator protein (GM2AP) is a lysosomal lipid transfer with important biological roles in ganglioside catabolism, phospholipid metabolism, and T-cell activation. Previous studies of crystal structures GM2AP complexed the physiological ligand GM2 platelet activating factor (PAF) have shown binding at two specific locations within spacious apolar pocket an ordering effect endogenous resident lipids. To investigate structural basis further, was cocrystallized phosphatidylcholine (PC),...