Cingolani Gino, Bednenko Janna, Gillespie Matthew T, Gerace Larry
Departments of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Mol Cell. 2002 Dec;10(6):1345-53. doi: 10.1016/s1097-2765(02)00727-x.
Nuclear import of proteins containing a classical nuclear localization signal (NLS) involves NLS recognition by importin alpha, which associates with importin beta via the IBB domain. Other proteins, including parathyroid hormone-related protein (PTHrP), are imported into the nucleus by direct interaction with importin beta. We solved the crystal structure of a fragment of importin beta-1 (1-485) bound to the nonclassical NLS of PTHrP. The structure reveals a second extended cargo binding site on importin beta distinct from the IBB domain binding site. Using a permeabilized cell import assay we demonstrate that importin beta (1-485) can import PTHrP-coupled cargo in a Ran-dependent manner. We propose that this region contains a prototypical nuclear import receptor domain, which could have evolved into the modern importin beta superfamily.
含有经典核定位信号（NLS）的蛋白质的核输入涉及importin α对NLS的识别，importin α通过IBB结构域与importin β结合。其他蛋白质，包括甲状旁腺激素相关蛋白（PTHrP），通过与importin β直接相互作用而被导入细胞核。我们解析了与PTHrP的非经典NLS结合的importin β-1片段（1-485）的晶体结构。该结构揭示了importin β上与IBB结构域结合位点不同的第二个延伸的货物结合位点。使用通透细胞输入分析，我们证明importin β（1-485）可以以依赖Ran的方式输入PTHrP偶联的货物。我们提出该区域包含一个原型核输入受体结构域，它可能已经进化为现代的importin β超家族。
