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 bond

被引:115
作者
Lu, CF
Shimaoka, M
Ferzly, N
Oxvig, C
Takagi, J
Springer, TA
机构
[1] Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA
关键词
D O I
10.1073/pnas.041606398
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We introduced disulfide bonds to lock the integrin alphaL beta2 I domain in predicted open, ligand binding or closed, nonbinding conformations. Transfectants expressing alphaL beta2 heterodimers containing locked-open but not locked-closed or wild-type I domains constitutively adhered to intercellular adhesion molecule-1 (ICAM-1) substrates. Locking the I domain closed abolished constitutive and activatable adhesion. The isolated locked-open I domain bound as well as the activated alphaL beta2 heterodimer, and binding was abolished by reduction of the disulfide, Lovastatin, which binds under the conformationally mobile C-terminal alpha -helix of the I domain, inhibited binding to ICAM-1 by alphaL beta2 with wild-type, but not locked-open I domains. These data establish the importance of conformational change in the alphaL I domain for adhesive function and show that this domain is sufficient for full adhesive activity.
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页码:2387 / 2392
页数:6
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