Jiang Pengju, Campbell Iain D
Biochemistry Department, University of Oxford, Oxford, UK.
Biochemistry. 2008 Oct 21;47(42):11055-61. doi: 10.1021/bi8011466. Epub 2008 Sep 26.
Filamin, a large modular protein composed mainly of many immunoglobulin-like domains, is a potent cross-linker of actin filaments. The region containing immunoglobulin type modules 19-21 makes up the binding site for the cytoplasmic tails of the integrin adhesion receptors. Here we investigate the stability of the Ig-like filamin domains using NMR studies over a range of pH and temperature. We show that the 21st Ig-like module (FLNa21) is partly unfolded even under physiological conditions and when attached to FLNa20. It is, however, appreciably stabilized upon binding to integrins. FLNa21 is noticeably less stable than neighboring homologous modules, such as FLNa19 and FLNa17. This variability in stability could be related to the known sensitivity of filamin to cell-mediated mechanical forces.
细丝蛋白是一种主要由许多免疫球蛋白样结构域组成的大型模块化蛋白质，是肌动蛋白丝的有效交联剂。包含免疫球蛋白类型模块19 - 21的区域构成整合素粘附受体细胞质尾巴的结合位点。在此，我们通过在一系列pH值和温度条件下的核磁共振研究来探究免疫球蛋白样细丝蛋白结构域的稳定性。我们发现，即使在生理条件下且与细丝蛋白A20（FLNa20）相连时，第21个免疫球蛋白样模块（FLNa21）也会部分展开。然而，在与整合素结合后，它会明显稳定下来。FLNa21的稳定性明显低于相邻的同源模块，如FLNa19和FLNa17。这种稳定性的差异可能与细丝蛋白对细胞介导的机械力的已知敏感性有关。
