Institut für Strukturbiologie und Biophysik 3 (Strukturbiochemie), Forschungszentrum Jülich, 52425 Jülich, Germany.
Proteins. 2009 Nov 15;77(3):637-46. doi: 10.1002/prot.22477.
Vesicular trafficking is an important homeostatic process in eukaryotic cells which critically relies on membrane fusion. One of the essential components of the universal membrane fusion machinery is NSF (N-ethylmaleimide-sensitive factor), a large hexameric ATPase involved in disassembly of SNARE (soluble NSF attachment protein receptor) complexes. To improve our understanding of this sophisticated molecular machine, we have modeled the structure of the NSF hexamer in two alternative assemblies. Our data suggest a mechanistic concept of the operating mode of NSF which helps to explain the functional impact of post-translational modifications and mutations reported previously. Furthermore, we propose a binding site for the ubiquitin-like proteins GABARAP and GATE-16, which is supported by experimental evidence, yielding a complex with favorable surface complementarity.
囊泡运输是真核细胞中的一种重要的动态平衡过程，其关键依赖于膜融合。普遍的膜融合机制的基本组件之一是 NSF（N-乙基马来酰亚胺敏感因子），一种涉及 SNARE（可溶性 NSF 附着蛋白受体）复合物解体的大型六聚体 ATP 酶。为了更好地理解这个复杂的分子机器，我们已经对 NSF 六聚体的两种替代构象进行了建模。我们的数据提出了 NSF 工作模式的一种机械概念，有助于解释先前报道的翻译后修饰和突变的功能影响。此外，我们提出了一个与泛素样蛋白 GABARAP 和 GATE-16 结合的位点，该位点得到了实验证据的支持，产生了一个具有良好表面互补性的复合物。
