Department of Cancer Biology, The Scripps Research Institute, Jupiter, Florida 33458, USA.
J Biol Chem. 2010 Apr 16;285(16):11983-90. doi: 10.1074/jbc.M109.092049. Epub 2010 Feb 2.
Sorting nexin 9 (SNX9) functions in a complex with the GTPase dynamin-2 at clathrin-coated pits, where it provokes fission of vesicles to complete endocytosis. Here the SNX9.dynamin-2 complex binds to clathrin and adapter protein complex 2 (AP-2) that line these pits, and this occurs through interactions of the low complexity domain (LC4) of SNX9 with AP-2. Intriguingly, localization of the SNX9.dynamin-2 complex to clathrin-coated pits is blocked by interactions with the abundant glycolytic enzyme aldolase, which also binds to the LC4 domain of SNX9. The crystal structure of the LC4 motif of human SNX9 in complex with aldolase explains the biochemistry and biology of this interaction, where SNX9 binds near the active site of aldolase via residues 165-171 that are also required for the interactions of SNX9 with AP-2. Accordingly, SNX9 binding to aldolase is structurally precluded by the binding of substrate to the active site. Interactions of SNX9 with aldolase are far more extensive and differ from those of the actin-nucleating factor WASP with aldolase, indicating considerable plasticity in mechanisms that direct the functions of the aldolase as a scaffold protein.
分选连接蛋白 9（SNX9）在网格蛋白包被凹陷处与 GTP 酶 dynamin-2 形成复合物，在此处它引发囊泡的裂变以完成内吞作用。在此，SNX9.dynamin-2 复合物与包被这些凹陷的网格蛋白和衔接蛋白复合物 2（AP-2）结合，这是通过 SNX9 的低复杂度结构域（LC4）与 AP-2 的相互作用实现的。有趣的是，SNX9.dynamin-2 复合物向网格蛋白包被凹陷处的定位被与丰富的糖酵解酶醛缩酶的相互作用所阻断，醛缩酶也与 SNX9 的 LC4 结构域结合。人 SNX9 的 LC4 基序与醛缩酶复合物的晶体结构解释了这种相互作用的生物化学和生物学，其中 SNX9 通过残基 165-171 结合到醛缩酶的活性位点，这些残基对于 SNX9 与 AP-2 的相互作用也是必需的。因此，由于底物与活性位点的结合，SNX9 与醛缩酶的结合在结构上被排除。SNX9 与醛缩酶的相互作用要广泛得多，与肌动蛋白成核因子 WASP 与醛缩酶的相互作用不同，这表明作为支架蛋白的醛缩酶指导其功能的机制具有相当大的灵活性。
