Qiang Chen

Harvard University, Cambridge, Massachusetts, United States

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Publications (3)10.81 Total impact

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    ABSTRACT: DCC (Deleted in Colorectal Cancer) is a receptor for axon guidance cues netrin-1 and draxin. The interactions between these guidance cues and DCC play a key role in the development of the nervous system. Here, we present the crystal structure of the N-terminal four Ig-like domains of DCC. The molecule folds into a horseshoe-like configuration. We demonstrate that this horseshoe conformation of DCC is required for guidance cue mediated axonal attraction. Structure-based mutations that disrupt the DCC horseshoe indeed impair its function. A comparison of the DCC horseshoe with previously described horseshoe structures has revealed striking conserved structural features and important sequence signatures. Using these signatures a genome-wide search allows us to predict the N-terminal horseshoe arrangement in a number of other cell surface receptors, which nearly all function in the nervous system. The N-terminal horseshoe appears to be evolutionally selected as a platform for neural receptors.
    Journal of Cell Science 10/2012; 126(1). DOI:10.1242/jcs.111278 · 5.33 Impact Factor
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    ABSTRACT: Developmental endothelial cell locus-1 (Del-1) glycoprotein is secreted by endothelial cells and a subset of macrophages. Del-1 plays a regulatory role in vascular remodeling and functions in innate immunity through interaction with integrin α(V)β(3). Del-1 contains 3 epidermal growth factor (EGF)-like repeats and 2 discoidin-like domains. An Arg-Gly-Asp (RGD) motif in the second EGF domain (EGF2) mediates adhesion by endothelial cells and phagocytes. We report the crystal structure of its 3 EGF domains. The RGD motif of EGF2 forms a type II' β turn at the tip of a long protruding loop, dubbed the RGD finger. Whereas EGF2 and EGF3 constitute a rigid rod via an interdomain calcium ion binding site, the long linker between EGF1 and EGF2 lends considerable flexibility to EGF1. Two unique O-linked glycans and 1 N-linked glycan locate to the opposite side of EGF2 from the RGD motif. These structural features favor integrin binding of the RGD finger. Mutagenesis data confirm the importance of having the RGD motif at the tip of the RGD finger. A database search for EGF domain sequences shows that this RGD finger is likely an evolutionary insertion and unique to the EGF domain of Del-1 and its homologue milk fat globule-EGF 8.
    The FASEB Journal 05/2012; 26(8):3412-20. DOI:10.1096/fj.11-202036 · 5.48 Impact Factor
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    ABSTRACT: The αβ T cell receptor (TCR) is a multimeric complex whose β chain plays a crucial role in thymocyte development as well as antigen recognition by mature T lymphocytes. We report here crystal structures of individual β subunits, termed N15β (Vβ5.2Dβ2Jβ2.6Cβ2) and N30β (Vβ13Dβ1Jβ1.1Cβ2), derived from two αβ TCRs specific for the immunodominant vesicular stomatitis virus octapeptide (VSV-8) bound to the murine H-2K(b) MHC class I molecule. The crystal packing of the N15β structure reveals a homodimer formed through two Vβ domains. The Vβ/Vβ module is topologically very similar to the Vα/Vβ module in the N15αβ heterodimer. By contrast, in the N30β structure, the Vβ domain's external hydrophobic CFG face is covered by the neighboring molecule's Cβ domain. In conjunction with systematic investigation of previously published TCR single-subunit structures, we identified several conserved residues forming a concave hydrophobic patch at the center of the CFG outer face of the Vβ and other V-type Ig-like domains. This hydrophobic patch is shielded from solvent exposure in the crystal packing, implying that it is unlikely to be thermodynamically stable if exposed on the thymocyte surface. Accordingly, we propose a dimeric pre-TCR model distinct from those suggested previously by others and discuss its functional and structural implications.
    Frontiers in Immunology 03/2011; 2:5. DOI:10.3389/fimmu.2011.00005

Publication Stats

12 Citations
10.81 Total Impact Points


  • 2012
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2011
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States