Ns, talin, and kindlins. Science 324, 895899 18. Kim, C., Ye, F., and Ginsberg

Ns, talin, and kindlins. Science 324, 895899 18. Kim, C., Ye, F., and Ginsberg, M. H. (2011) Regulation of integrin activation. Annu. Rev. Cell Dev. Biol. 27, 32145 19. Zhang, K., and Chen, J. (2012) The regulation of integrin function by divalent cations. Cell Adh. Migr. 6, 20 9 20. Mould, A. P., Akiyama, S. K., and Humphries, M. J. (1995) Regulation of integrin five 1-fibronectin interactions by divalent cations. Evidence for distinct classes of binding web pages for Mn2 , Mg2 , and Ca2 . J. Biol. Chem. 270, 26270 6277 21. Leitinger, B., McDowall, A., Stanley, P., and Hogg, N. (2000) The regulation of integrin function by Ca(2 ). Biochim. Biophys. Acta 1498, 918 22. de Ch eau, M., Chen, S., Salas, A., and Springer, T. A. (2001) Kinetic and mechanical basis of rolling by means of an integrin and novel Ca2 -dependent rolling and Mg2 -dependent firm adhesion modalities for the 4 7MAdCAM-1 interaction. Biochemistry 40, 139723979 23. Xiong, J. P., Stehle, T., Zhang, R., Joachimiak, A., Frech, M., Goodman, S. L., and Arnaout, M. A. (2002) Crystal structure on the extracellular segment of integrin V 3 in complicated with an Arg-Gly-Asp ligand. Science 296, 15155 24. Xiong, J. P., Mahalingham, B., Alonso, J. L., Borrelli, L. A., Rui, X., Anand, S., Hyman, B. T., Rysiok, T., M ler-Pompalla, D., Goodman, S. L., and Arnaout, M. A. (2009) Crystal structure in the complete integrin V 3 ectodomain plus an / transmembrane fragment.Tirofiban J.Bufuralol Cell Biol.PMID:23453497 186, 589 600 25. Zhu, J., Luo, B. H., Xiao, T., Zhang, C., Nishida, N., and Springer, T. A. (2008) Structure of a complete integrin ectodomain within a physiologic resting state and activation and deactivation by applied forces. Mol. Cell 32, 849 861 26. Sun, H., Wu, Y., Qi, J., Pan, Y., Ge, G., and Chen, J. (2011) The CC’ and DE loops in Ig domains 1 and two of MAdCAM-1 play various roles in MAdCAM-1 binding to low- and high-affinity integrin four 7. J. Biol. Chem. 286, 12086 2092 27. Pan, Y., Zhang, K., Qi, J., Yue, J., Springer, T. A., and Chen, J. (2010) Cation- interaction regulates ligand-binding affinity and signaling of integrin 4 7. Proc. Natl. Acad. Sci. U.S.A. 107, 21388 1393 28. Yu, Y., Zhu, J., Mi, L. Z., Walz, T., Sun, H., Chen, J., and Springer, T. A. (2012) Structural specializations of four 7, an integrin that mediates rolling adhesion. J. Cell Biol. 196, 13146 29. Lazarovits, A. I., Moscicki, R. A., Kurnick, J. T., Camerini, D., Bhan, A. K.,FIGURE 7. Effect in the W1 4- 1 loop mutations around the adhesive modality of integrin four 7, four 1, and 9 1 on VCAM-1 substrates in shear flow. A, rolling and firm adhesions of WT and mutant four 7 293T transient transfectants on immobilized VCAM-1 substrates (ten g/ml) in 1 mM Ca2 /Mg2 or 0.five mM Mn2 . B, rolling and firm adhesions of WT and mutant four 1 293T transient transfectants on immobilized VCAM-1 substrates (3.5 g/ml) in 1 mM Ca2 /Mg2 or 0.five mM Mn2 . C, rolling and firm adhesions of WT and mutant 9 1 293T transient transfectants on immobilized VCAM-1 substrates (20 g/ml) in 1 mM Ca2 /Mg2 or 0.5 mM Mn2 . The amount of rolling and firmly adherent WT and mutant transfectants was measured in the indicated divalent cations at a wall shear strain of 2 dynes/cm2. Cells treated with 5 mM EDTA have been utilised as a handle. Data are mean S.E. (n 3). p values have been calculated by one-way ANOVA with Dunnett post-tests. **, p 0.01; ***, p 0.001.illin, indicating that four 7-mediated outside-in signaling also needs the typical function of your W1 4- 1 loop. Therefore, the disulfide bond-stabilized W1 4- 1 loop.