Dong Mingdong, Xu Sailong, Oliveira Cristiano L P, Pedersen Jan S, Thiel Steffen, Besenbacher Flemming, Vorup-Jensen Thomas
Interdisciplinary Nanoscience Center (iNANO), Department of Physiucs and Astronomy, University of Aarhus, Aarhus C, Denmark.
J Immunol. 2007 Mar 1;178(5):3016-22. doi: 10.4049/jimmunol.178.5.3016.
The binding of soluble proteins to target surfaces is vital in triggering the immune response. However, structural insight into such processes is still lacking. Mannan-binding lectin (MBL) is a classic example of a pattern recognition molecule with important roles in innate immunity against microbial infections. By small angle x-ray scattering analysis we show that the large MBL complex in solution is folded into a ramified structure with a striking rotational symmetry and a structure permissive of elongation by unbending. Nevertheless, the structure in solution is found to be very stable. However, when the MBL molecule interacts with surface-immobilized ligands, the stable MBL structure is broken into a stretched state with separation of the ligand-binding domains as shown by high resolution atomic force microscopy. These studies provide a snapshot of the single molecule mechanics of MBL and the first direct evidence that the transition from the soluble state to surface-bound protein involves large conformational changes in the quaternary structure, thus highlighting the role of surface topography in immune recognition.
可溶性蛋白质与靶表面的结合对于触发免疫反应至关重要。然而，目前仍缺乏对这类过程的结构洞察。甘露聚糖结合凝集素（MBL）是一种模式识别分子的经典例子，在针对微生物感染的固有免疫中发挥着重要作用。通过小角X射线散射分析，我们表明溶液中的大型MBL复合物折叠成具有显著旋转对称性的分支结构，并且具有通过伸直实现伸长的结构。尽管如此，溶液中的结构被发现非常稳定。然而，当MBL分子与表面固定的配体相互作用时，如高分辨率原子力显微镜所示，稳定的MBL结构会分解成伸展状态，配体结合结构域分离。这些研究提供了MBL单分子力学的一个快照，以及第一个直接证据，即从可溶状态到表面结合蛋白的转变涉及四级结构的大构象变化，从而突出了表面形貌在免疫识别中的作用。
