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T cell receptor cross-linking transiently stimulates adhesiveness through LFA-1
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Humphries M.J., McEwan P.A., Askari J.A., Barton S.J., Buckley P.A., Craig S.E., Bella J., Mould A.P. Integrin structure: heady advances in ligand binding, but activation still makes the knees wobble. Trends Biochem Sci. 28:2003;313-320.
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Takagi J., Springer T.A. Integrin activation and structural rearrangement. Immunol Rev. 186:2002;141-163.
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Takagi, J.1
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0024293497
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Electron microscopy and structural model of human fibronectin receptor
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8
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Crystal structure of the extracellular segment of integrin αVβ3
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This is the watershed description of the structure of most of the integrin extracellular domain, which displayed an unexpected V-shaped topology arising from a severe bend in the stalks termed the 'genu'.
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Xiong J.-P., Stehle T., Diefenbach B., Zhang R., Dunker R., Scott D.L., Joachimiak A., Goodman S.L., Arnaout M.A. Crystal structure of the extracellular segment of integrin αVβ3. Science. 294:2001;339-345 This is the watershed description of the structure of most of the integrin extracellular domain, which displayed an unexpected V-shaped topology arising from a severe bend in the stalks termed the 'genu'.
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Xiong, J.-P.1
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Association of the membrane-proximal regions of the α and β subunit cytoplasmic domains constrains an integrin in the inactive state
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Lu C., Takagi J., Springer T.A. Association of the membrane-proximal regions of the α and β subunit cytoplasmic domains constrains an integrin in the inactive state. J Biol Chem. 276:2001;14642-14648.
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Lu, C.1
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Cysteine-rich module structure reveals a fulcrum for integrin rearrangement upon activation
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•• ]. Localization of activation epitopes to sterically inaccessible surfaces in the bent integrin suggested that this conformation represents the low-affinity state. A switchblade-like rearrangement was suggested to occur during activation that would make the epitopes accessible for antibody recognition.
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••]. Localization of activation epitopes to sterically inaccessible surfaces in the bent integrin suggested that this conformation represents the low-affinity state. A switchblade-like rearrangement was suggested to occur during activation that would make the epitopes accessible for antibody recognition.
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Beglova, N.1
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11
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0037031906
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Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling
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2+ induced a switchblade-like extension of the integrin, with a mixture of closed and open headpiece orientations. Cyclic RGD exclusively produced the extended conformer with the open headpiece. Stabilization of the bent conformation on the cell surface by an engineered disulfide bond prevented activation.
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2+ induced a switchblade-like extension of the integrin, with a mixture of closed and open headpiece orientations. Cyclic RGD exclusively produced the extended conformer with the open headpiece. Stabilization of the bent conformation on the cell surface by an engineered disulfide bond prevented activation.
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Cell
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Takagi, J.1
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12
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0035041854
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C-terminal opening mimics 'inside-out' activation of integrin α5β1
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Rotary-shadowed electron microscopy, together with surface plasmon resonance and solid-phase equilibrium ligand-binding studies, were performed on soluble extracellular domain α5β1 heterodimer with an engineered protease-cleavable clasp replacing the transmembrane and cytoplasmic domains. Release of the clasp induced a substantial separation of the stalks that was coupled to a significant increase in affinity for ligand.
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Takagi J., Erickson H.P., Springer T.A. C-terminal opening mimics 'inside-out' activation of integrin α5β1. Nat Struct Biol. 8:2001;412-416 Rotary-shadowed electron microscopy, together with surface plasmon resonance and solid-phase equilibrium ligand-binding studies, were performed on soluble extracellular domain α5β1 heterodimer with an engineered protease-cleavable clasp replacing the transmembrane and cytoplasmic domains. Release of the clasp induced a substantial separation of the stalks that was coupled to a significant increase in affinity for ligand.
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Nat Struct Biol
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Takagi, J.1
Erickson, H.P.2
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13
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0033561096
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A mutation in the extracellular cysteine-rich repeat region of the β3 subunit activates integrins αIIbβ3 and αVβ3
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Kashiwagi H., Tomiyama Y., Tadokoro S., Honda S., Shiraga M., Mizutani H., Handa M., Kurata Y., Matsuzawa Y., Shattil S.J. A mutation in the extracellular cysteine-rich repeat region of the β3 subunit activates integrins αIIbβ3 and αVβ3. Blood. 93:1999;2559-2568.
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Kashiwagi, H.1
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14
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0037418254
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Stabilizing the open conformation of the integrin headpiece with a glycan wedge increases affinity for ligand
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Ectopic N-linked glycosylation sites were mutationally introduced into a loop at the bottom of the β1 and β3 I-like domains to serve as 'wedges', enforcing the open headpiece conformation. In the context of α5β1 and αIIβ3, these mutations induced constitutive high affinity for ligand. A model for I-like domain activation, driven by downward translation of the carboxy-terminal helix and swing-out of the hybrid domain, was suggested.
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Luo B.-H., Springer T.A., Takagi J. Stabilizing the open conformation of the integrin headpiece with a glycan wedge increases affinity for ligand. Proc Natl Acad Sci USA. 100:2003;2403-2408 Ectopic N-linked glycosylation sites were mutationally introduced into a loop at the bottom of the β1 and β3 I-like domains to serve as 'wedges', enforcing the open headpiece conformation. In the context of α5β1 and αIIβ3, these mutations induced constitutive high affinity for ligand. A model for I-like domain activation, driven by downward translation of the carboxy-terminal helix and swing-out of the hybrid domain, was suggested.
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Proc Natl Acad Sci USA
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Luo, B.-H.1
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Takagi, J.3
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Structural basis of collagen recognition by integrin α2β1
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0037428080
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Structures of the αL I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation
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Shimaoka M., Xiao T., Liu J.-H., Yang Y., Dong Y., Jun C.-D., McCormack A., Zhang R., Joachimiak A., Takagi J.et al. Structures of the αL I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation. Cell. 112:2003;99-111.
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Shimaoka, M.1
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Jun, C.-D.6
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Zhang, R.8
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0035956969
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An isolated, surface-expressed I domain of the integrin αLβ2 is sufficient for strong adhesive function when locked in the open conformation with a disulfide
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Lu C., Shimaoka M., Ferzly M., Oxvig C., Takagi J., Springer T.A. An isolated, surface-expressed I domain of the integrin αLβ2 is sufficient for strong adhesive function when locked in the open conformation with a disulfide. Proc Natl Acad Sci USA. 98:2001;2387-2392.
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Lu, C.1
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21
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0035956887
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Locking in alternate conformations of the integrin αLβ2 I domain with disulfide bonds reveals functional relationships among integrin domains
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Lu C., Shimaoka M., Zang Q., Takagi J., Springer T.A. Locking in alternate conformations of the integrin αLβ2 I domain with disulfide bonds reveals functional relationships among integrin domains. Proc Natl Acad Sci USA. 98:2001;2393-2398.
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Proc Natl Acad Sci USA
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Lu, C.1
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22
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0033900165
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Computational design of an integrin I domain stabilized in the open, high affinity conformation
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Shimaoka M., Shifman J.M., Jing H., Takagi J., Mayo S.L., Springer T.A. Computational design of an integrin I domain stabilized in the open, high affinity conformation. Nat Struct Biol. 7:2000;674-678.
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Nat Struct Biol
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Shimaoka, M.1
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Springer, T.A.6
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23
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0035932996
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Reversibly locking a protein fold in an active conformation with a disulfide bond: Integrin αL I domains with high affinity and antagonist activity in vivo
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Disulfide bonds that bracket the carboxy-terminal β6-α7 loop and stabilize the open conformation of the αL I domain result in a 10,000-fold increase in affinity for ICAM-1, as determined by surface plasmon resonance.
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Shimaoka M., Lu C., Palframan R., von Andrian U.H., Takagi J., Springer T.A. Reversibly locking a protein fold in an active conformation with a disulfide bond: integrin αL I domains with high affinity and antagonist activity in vivo. Proc Natl Acad Sci USA. 98:2001;6009-6014 Disulfide bonds that bracket the carboxy-terminal β6-α7 loop and stabilize the open conformation of the αL I domain result in a 10,000-fold increase in affinity for ICAM-1, as determined by surface plasmon resonance.
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Shimaoka, M.1
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24
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0037168524
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Stabilizing the integrin αM inserted domain in alternative conformations with a range of engineered disulfide bonds
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Shimaoka M., Lu C., Salas A., Xiao T., Takagi J., Springer T.A. Stabilizing the integrin αM inserted domain in alternative conformations with a range of engineered disulfide bonds. Proc Natl Acad Sci USA. 99:2002;16737-16741.
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Shimaoka, M.1
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25
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0034624058
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An isoleucine-based allosteric switch controls affinity and shape shifting in integrin CD11b A-domain
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Xiong J.-P., Li R., Essafi M., Stehle T., Arnaout M.A. An isoleucine-based allosteric switch controls affinity and shape shifting in integrin CD11b A-domain. J Biol Chem. 275:2000;38762-38767.
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Xiong, J.-P.1
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Arnaout, M.A.5
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26
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0037452666
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Structure and allosteric regulation of the αXβ2 integrin I domain
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Vorup-Jensen T., Shimaoka M., Ostermeier C., Hommel U., Springer T.A. Structure and allosteric regulation of the αXβ2 integrin I domain. Proc Natl Acad Sci USA. 100:2003;1873-1878.
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Proc Natl Acad Sci USA
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Vorup-Jensen, T.1
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27
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0033515012
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Conformational changes in tertiary structure near the ligand binding site of an integrin I domain
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Oxvig C., Lu C., Springer T.A. Conformational changes in tertiary structure near the ligand binding site of an integrin I domain. Proc Natl Acad Sci USA. 96:1999;2215-2220.
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28
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0037155910
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Activation induced conformational changes in the I domain region of LFA-1
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Ma Q., Shimaoka M., Lu C., Jing H., Carman C.V., Springer T.A. Activation induced conformational changes in the I domain region of LFA-1. J Biol Chem. 277:2002;10638-10641.
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Ma, Q.1
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29
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0032922549
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A novel leukocyte adhesion deficiency caused by expressed but nonfunctional β2 integrins Mac-1 and LFA-1
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Hogg N., Stewart M.P., Scarth S.L., Newton R., Shaw J.M., Law S.K.A., Klein N. A novel leukocyte adhesion deficiency caused by expressed but nonfunctional β2 integrins Mac-1 and LFA-1. J Clin Invest. 103:1999;97-106.
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Klein, N.7
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0141746138
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Small molecule integrin antagonists that bind to the β2 subunit I-like domain and activate signals in one direction and block them in another
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in press
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Shimaoka M, Salas A, Yang W, Weitz-Schmidt G, Springer TA: Small molecule integrin antagonists that bind to the β2 subunit I-like domain and activate signals in one direction and block them in another. Immunity 2003, in press.
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Immunity
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Shimaoka, M.1
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Yang, W.3
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0037076494
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Does the integrin αA domain act as a ligand for its βA domain?
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Alonso J.L., Essafi M., Xiong J.P., Stehle T., Arnaout M.A. Does the integrin αA domain act as a ligand for its βA domain? Curr Biol. 12:2002;R340-R342.
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0034625083
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NMR and mutagenesis evidence for an I domain allosteric site that regulates lymphocyte function-associated antigen 1 ligand binding
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Huth J.R., Olejniczak E.T., Mendoza R., Liang H., Harris E.A., Lupher M.L. Jr., Wilson A.E., Fesik S.W., Staunton D.E. NMR and mutagenesis evidence for an I domain allosteric site that regulates lymphocyte function-associated antigen 1 ligand binding. Proc Natl Acad Sci USA. 97:2000;5231-5236.
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Conformational changes in the integrin βA domain provide a mechanism for signal transduction via hybrid domain movement
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Mould AP, Barton SJ, Askari JA, McEwan PA, Buckley PA, Craig SE, Humphries MJ: Conformational changes in the integrin βA domain provide a mechanism for signal transduction via hybrid domain movement. J Biol Chem 2003, in press.
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Mould, A.P.1
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0037195164
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Three-dimensional model of the human platelet integrin αIIbβ3 based on electron cryomicroscopy and X-ray crystallography
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Adair B.D., Yeager M. Three-dimensional model of the human platelet integrin αIIbβ3 based on electron cryomicroscopy and X-ray crystallography. Proc Natl Acad Sci USA. 99:2002;14059-14064.
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0037031551
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3 'inside-out' activation as regulated by its cytoplasmic face
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Nuclear magnetic resonance structural analysis demonstrated the formation of a direct association between the αIIb and β3 cytoplasmic tails that was disrupted by the talin head domain and activating mutations.
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3 'inside-out' activation as regulated by its cytoplasmic face. Cell. 110:2002;587-597 Nuclear magnetic resonance structural analysis demonstrated the formation of a direct association between the αIIb and β3 cytoplasmic tails that was disrupted by the talin head domain and activating mutations.
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Vinogradova, O.1
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0042681786
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Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins
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Kim M, Carman CV, Springer TA: Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science 2003, in press.
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Science
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Kim, M.1
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Luo B.-H., Springer T.A., Takagi J. High affinity ligand binding by integrins does not involve head separation. J Biol Chem. 278:2003;17185-17189.
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Flow cytometric measurement of kinetic and equilibrium binding parameters of arginine-glycine-aspartic acid ligands in binding to glycoprotein IIb/IIIa on platelets
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Two-step binding mechanism of fibrinogen to alpha IIb beta 3 integrin reconstituted into planar lipid bilayers
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Determination of kinetic constants for the interaction between the platelet glycoprotein IIb-IIIa and fibrinogen by means of surface plasmon resonance
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Chemokines trigger immediate β2 integrin affinity and mobility changes: Differential regulation and roles in lymphocyte arrest under flow
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Constantin G., Majeed M., Giagulli C., Piccib L., Kim J.Y., Butcher E.C., Laudanna C. Chemokines trigger immediate β2 integrin affinity and mobility changes: differential regulation and roles in lymphocyte arrest under flow. Immunity. 13:2000;759-769.
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Chemoattractants induce rapid and transient upregulation of monocyte alpha4 integrin affinity for vascular adhesion molecule 1 which mediates arrest: An early step in the process of emigration
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Chan J.R., Hyduk S.J., Cybulsky M.I. Chemoattractants induce rapid and transient upregulation of monocyte alpha4 integrin affinity for vascular adhesion molecule 1 which mediates arrest: an early step in the process of emigration. J Exp Med. 193:2001;1149-1158.
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Crystal structure of the extracellular segment of integrin αVβ3 in complex with an Arg-Gly-Asp ligand
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By soaking a cyclic-RGD peptide ligand into a crystal of αVβ3 the details of the ligand-binding site are identified. While the aspartate sidechain coordinated to the metal in the MIDAS of the I-like domain of the β3 subunit, the arginine formed salt bridges with loops in blades 2 and 3 of the β-propeller domain of the αV subunit.
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Xiong J.P., Stehle T., Zhang R., Joachimiak A., Frech M., Goodman S.L., Arnaout M.A. Crystal structure of the extracellular segment of integrin αVβ3 in complex with an Arg-Gly-Asp ligand. Science. 296: 2002;151-155 By soaking a cyclic-RGD peptide ligand into a crystal of αVβ3 the details of the ligand-binding site are identified. While the aspartate sidechain coordinated to the metal in the MIDAS of the I-like domain of the β3 subunit, the arginine formed salt bridges with loops in blades 2 and 3 of the β-propeller domain of the αV subunit.
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(2002)
Science
, vol.296
, pp. 151-155
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Xiong, J.P.1
Stehle, T.2
Zhang, R.3
Joachimiak, A.4
Frech, M.5
Goodman, S.L.6
Arnaout, M.A.7
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86
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0026554716
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Regulation of locomotion and cell-cell contact area by the LFA-1 and ICAM-1 adhesion receptors
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Dustin M.L., Carpen O., Springer T.A. Regulation of locomotion and cell-cell contact area by the LFA-1 and ICAM-1 adhesion receptors. J Immunol. 148:1992;2654-2663.
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(1992)
J Immunol
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, pp. 2654-2663
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Dustin, M.L.1
Carpen, O.2
Springer, T.A.3
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