Our laboratory focuses on solving the three-dimensional (3D) structure of biologically important macromolecules at atomic resolution using X-ray protein crystallographic techniques. The resulting 3D structures allow us to better understand the structure-function relationship of these molecules when combined with other molecular and cellular biological approaches. They can also provide critical information for structure-based drug design. More specifically, we target on structural elucidation of a class of cellur adhesion receptors called integrins, which are involved in various human ailments including glomerulonephritis, allograft rejection, heart attacks, restenosis, cancer, arthritis, and infection. We are also working to develop a new class of anti-integrin drugs with more efficiency but fewer adverse effects using the 3D models we have generated.

References

  1. Xiong JP, Stehle T, Diefenbach B, Zhang R, Dunker R, Scott DL, Joachimiak A, Goodman SL, and Arnaout MA. Crystal structure of the extracellular segment of integrin alpha Vbeta 3. Science. 2001; 294(5541): 339-345.
  2. Xiong JP, Stehle T, Zhang R, Joachimiak A, Frech M, Goodman SL, and Arnaout MA. Crystal structure of the extracellular segment of integrin alpha Vbeta3 in complex with an Arg-Gly-Asp ligand. Science.2002; 296(5565): 151-5.
  3. Xiong JP, Stehle T, Goodman SL, and Arnaout MA. A novel adaptation of the integrin PSI domain revealed from its crystal structure. J Biol Chem.2004; 279(39): 40252 - 40254.
  4. Xiong JP, Mahalingham B, Alonso JL, Borrelli LA, Rui X, Anand S, Hyman BT, Rysiok T, Müller-Pompalla D, Goodman SL, Arnaout MA. Crystal structure of the complete integrin alphaVbeta3 ectodomain plus an alpha/beta transmembrane fragment. J Cell Biol.2009; 186(4):589-600.
  5. Van Agthoven JF, Xiong JP*, Alonso JL, Rui X, Adair BD, Goodman SL, Arnaout MA. Structural basis for pure antagonism of integrin αVβ3 by a high-affinity form of fibronectin. Nat Struct Mol Biol. 2014; 21(4):383-8
  6. Mahalingam B, Van Agthoven JF, Xiong JP, Alonso JL, Adair BD, Rui X, Anand S, Mehrbod M, Mofrad MR, Burger C, Goodman SL, Arnaout MA. Atomic basis for the species-specific inhibition of αV integrins by monoclonal antibody 17E6 is revealed by the crystal structure of αVβ3 ectodomain-17E6 Fab complex. J Biol Chem. 2014; 289(20):13801-9.
  7. Rui X, Mehrbod M, Van Agthoven JF, Anand S, Xiong JP, Mofrad MR, Arnaout MA. The α subunit regulates stability of the metal ion at the ligand-associated metal ion-binding site in β3 integrins. J Biol Chem. 2014; 289(33):23256-63.

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