Nielsen Tine K, Liu Sunbin, Lührmann Reinhard, Ficner Ralf
Abteilung für Molekulare Strukturbiologie, Institut für Mikrobiologie und Genetik, Georg-August-Universität Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany.
J Mol Biol. 2007 Jun 15;369(4):902-8. doi: 10.1016/j.jmb.2007.03.077. Epub 2007 Apr 4.
The bifunctional protein U5-52K is associated with the spliceosomal 20 S U5 snRNP, and it also plays a role in immune response as CD2 receptor binding protein 2 (CD2BP2). U5-52K binds to the CD2 receptor via its GYF-domain specifically recognizing a proline-rich motif on the cytoplasmic surface of the receptor. The GYF-domain is also mediating the interaction of the proteins U5-52K and U5-15K within the spliceosomal U5 snRNP. Here we report the crystal structure of the complex of GYF-domain and U5-15K protein revealing the structural basis for the bifunctionality of the U5-52K protein. The complex structure unveils novel interaction sites on both proteins, as neither the polyproline-binding site of the GYF-domain nor the common ligand-binding cleft of thioredoxin-like proteins, to which U5-15K belongs, are involved in the interaction of U5-15K and U5-52K.
双功能蛋白U5-52K与剪接体20S U5 snRNP相关，并且它作为CD2受体结合蛋白2（CD2BP2）在免疫反应中也发挥作用。U5-52K通过其GYF结构域与CD2受体结合，该结构域特异性识别受体细胞质表面富含脯氨酸的基序。GYF结构域还介导剪接体U5 snRNP内蛋白质U5-52K和U5-15K之间的相互作用。在此，我们报道了GYF结构域与U5-15K蛋白复合物的晶体结构，揭示了U5-52K蛋白双功能的结构基础。该复合物结构揭示了两种蛋白质上的新相互作用位点，因为GYF结构域的多聚脯氨酸结合位点和U5-15K所属的硫氧还蛋白样蛋白的常见配体结合裂隙均未参与U5-15K和U5-52K的相互作用。
