Small-angle neutron scattering reveals the assembly mode and oligomeric architecture of TET, a large, dodecameric aminopeptidase.
Small-angle neutron scattering reveals the assembly mode and oligomeric architecture of TET, a large, dodecameric aminopeptidase.
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小角中子散射揭示了 TET（一种大型十二聚氨肽酶）的组装模式和寡聚结构。
DOI：
10.1107/s1399004714018446
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Appolaire A
中科院分区：
文献类型：
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作者：
Appolaire A
蛋白质特异性自缔合成寡聚复合物是生物系统中优化和调节其功能的常见现象。然而，这些重要配合物的从头结构测定对于原子分辨率技术来说通常非常具有挑战性。此外，在同源寡聚复合物或具有非常相似结构单元的复合物的情况下，使用许多结构生物学技术很难确定亚基的各自位置及其组装途径。在这里，应用了一种基于小角中子散射的优雅而强大的方法，结合氘标记和对比度变化，阐明了四级结构的寡聚组织以及 468 kDa、异源寡聚和对称 Pyrococcus horikoshii TET2-TET3 氨肽酶复合物的组装途径。结果表明，复合物中 PhTET2 和 PhTET3 二聚体结构单元的拓扑结构不是随意的，而是表明它们的四级排列优化了对肽底物的催化效率。该方法对于确定生物系统中大型寡聚和对称复合物的四级结构和组装途径具有重要潜力。
The specific self-association of proteins into oligomeric complexes is a common phenomenon in biological systems to optimize and regulate their function. However, de novo structure determination of these important complexes is often very challenging for atomic-resolution techniques. Furthermore, in the case of homo-oligomeric complexes, or complexes with very similar building blocks, the respective positions of subunits and their assembly pathways are difficult to determine using many structural biology techniques. Here, an elegant and powerful approach based on small-angle neutron scattering is applied, in combination with deuterium labelling and contrast variation, to elucidate the oligomeric organization of the quaternary structure and the assembly pathways of 468 kDa, hetero-oligomeric and symmetric Pyrococcus horikoshii TET2–TET3 aminopeptidase complexes. The results reveal that the topology of the PhTET2 and PhTET3 dimeric building blocks within the complexes is not casual but rather suggests that their quaternary arrangement optimizes the catalytic efficiency towards peptide substrates. This approach bears important potential for the determination of quaternary structures and assembly pathways of large oligomeric and symmetric complexes in biological systems.