整合素αLβ2的一个分离的、表面表达的I结构域，当通过二硫键锁定在开放构象时，足以发挥强大的黏附功能。
An isolated, surface-expressed I domain of the integrin alphaLbeta2 is sufficient for strong adhesive function when locked in the open conformation with a disulfide bond.
作者信息
Lu C, Shimaoka M, Ferzly M, Oxvig C, Takagi J, Springer T A
机构信息
The Center for Blood Research, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
出版信息
Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2387-92. doi: 10.1073/pnas.041606398.
Abstract
We introduced disulfide bonds to lock the integrin alphaLbeta2 I domain in predicted open, ligand binding or closed, nonbinding conformations. Transfectants expressing alphaLbeta2 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 alphaLbeta2 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 alphaLbeta2 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.
摘要
我们引入二硫键，将整合素αLβ2 I结构域锁定在预测的开放、配体结合构象或封闭、非结合构象中。表达含有锁定开放而非锁定封闭或野生型I结构域的αLβ2异二聚体的转染子可组成性地黏附于细胞间黏附分子-1（ICAM-1）底物。将I结构域锁定为封闭状态可消除组成性和可激活的黏附。分离的锁定开放I结构域的结合能力与激活的αLβ2异二聚体相当，且二硫键还原后结合被消除。洛伐他汀结合在I结构域构象可变的C末端α螺旋下方，可抑制具有野生型I结构域而非锁定开放I结构域的αLβ2与ICAM-1的结合。这些数据证实了αL I结构域构象变化对黏附功能的重要性，并表明该结构域足以实现完全的黏附活性。
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