Functional and structural correlations of individual αIIbβ3 molecules

Functional and structural correlations of individual αIIbβ3 molecules
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DOI:
10.1182/blood-2004-04-1411
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发表时间:
2004-12-15
期刊:
影响因子:
20.3
通讯作者:
Weisel, JW
Weisel, JW
中科院分区:
医学1区
文献类型:
--
作者:
Litvinov, RI;Nagaswami, C;Weisel, JW

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The divalent cation Mn2+ and the reducing agent dithiothreitol directly shift integrins from their inactive to their active states. We used transmission electron microscopy and laser tweezers-based force spectroscopy to determine whether structural rearrangements induced by these agents in the integrin alphallbbeta3 correlate with its ability to bind fibrinogen. Mn2+ increased the probability of specific fibrinogen-alphallbbeta3 interactions nearly 20-fold in platelets, and both Mn2+ and dithiothreitol increased the probability more tions exclusively involving the distal ends of the stalks. These results indicate that there is a direct correlation between alphallbbeta3 activation and the overall conformation of the molecule. Further, they are consistent with the presence of a linked equilibrium between single inactive and single active alphallbbeta3 molecules and active alphallbbeta3 clusters. (C) 2004 by The American Society of Hematology.