Walma Tine, Aelen Jan, Nabuurs Sander B, Oostendorp Marlies, van den Berk Lieke, Hendriks Wiljan, Vuister Geerten W
Department of Biophysical Chemistry, NSRIM Center, University of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands.
Structure. 2004 Jan;12(1):11-20. doi: 10.1016/j.str.2003.11.023.
PTP-BL is a large phosphatase that is implicated in cellular processes as diverse as cytokinesis, actin-cytoskeletal rearrangement, and apoptosis. Five PDZ domains mediate its cellular role by binding to the C termini of target proteins, forming multiprotein complexes. The second PDZ domain (PDZ2) binds to the C termini of the tumor suppressor protein APC and the LIM domain-containing protein RIL; however, in one splice variant, PDZ2as, a 5 residue insertion abrogates this binding. The insert causes distinct structural and dynamical changes in the alternatively spliced PDZ2: enlarging the L1 loop between beta2 and beta3, both lengthening and changing the orientation of the alpha2 helix, giving the base of the binding pocket less flexibility to accommodate ligands, and destabilizing the entire domain. These changes render the binding pocket incapable of binding C termini, possibly having implications in the functional role of PTP-BL.
PTP - BL是一种大型磷酸酶，参与多种细胞过程，如胞质分裂、肌动蛋白细胞骨架重排和细胞凋亡。五个PDZ结构域通过与靶蛋白的C末端结合来介导其细胞作用，形成多蛋白复合物。第二个PDZ结构域（PDZ2）与肿瘤抑制蛋白APC和含LIM结构域的蛋白RIL的C末端结合；然而，在一种剪接变体PDZ2as中，5个残基的插入消除了这种结合。该插入在选择性剪接的PDZ2中引起明显的结构和动力学变化：扩大β2和β3之间的L1环，延长并改变α2螺旋的方向，使结合口袋底部容纳配体的灵活性降低，并使整个结构域不稳定。这些变化使结合口袋无法结合C末端，这可能对PTP - BL的功能作用产生影响。
