Septins are membrane-associated, GTP-binding proteins that are present in most eukaryotes. They polymerize to play important roles as scaffolds and/or diffusion barriers as part of the cytoskeleton. α-Helical coiled-coil domains are believed to contribute to septin assembly, and those observed in both human SEPT6 and SEPT8 form antiparallel homodimers. These are not compatible with their parallel heterodimeric organization expected from the current model for protofilament assembly, but they could explain the interfilament cross-bridges observed by microscopy. Here, the first structure of a heterodimeric septin coiled coil is presented, that between SEPT14 and SEPT7; the former is a SEPT6/SEPT8 homolog. This new structure is parallel, with two long helices that are axially shifted by a full helical turn with reference to their sequence alignment. The structure also has unusual knobs-into-holes packing of side chains. Both standard seven-residue (heptad) and the less common 11-residue (hendecad) repeats are present, creating two distinct regions with opposite supercoiling, which gives rise to an overall straight coiled coil. Part of the hendecad region is required for heterodimerization and therefore may be crucial for selective septin recognition. These unconventional sequences and structural features produce a metastable heterocomplex that nonetheless has enough specificity to promote correct protofilament assembly. For instance, the lack of supercoiling may facilitate unzipping and transitioning to the antiparallel homodimeric state.

中文翻译：

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亚稳态SEPT14-SEPT7卷曲线圈的X射线结构揭示了对异二聚化至关重要的十六进制区域

Septin 是膜相关的 GTP 结合蛋白，存在于大多数真核生物中。它们聚合作为细胞骨架的一部分，作为支架和/或扩散屏障发挥重要作用。α-螺旋卷曲螺旋结构域被认为有助于 septin 组装，并且在人类 SEPT6 和 SEPT8 中观察到的结构域形成反平行同二聚体。这些与当前原丝组装模型预期的平行异二聚体组织不兼容，但它们可以解释通过显微镜观察到的丝间交叉桥。在这里，提出了异二聚体 septin 卷曲线圈的第一个结构，即 SEPT14 和 SEPT7 之间的结构；前者是 SEPT6/SEPT8 同系物。这种新结构是平行的，具有两个长螺旋，根据它们的序列对齐，它们轴向移动一整圈螺旋。该结构还具有不寻常的侧链旋钮入孔包装。标准的七残基（七肽）和不太常见的 11 残基（hendecad）重复都存在，形成两个具有相反超螺旋的不同区域，从而产生整体直卷曲螺旋。部分 hendecad 区域是异二聚化所必需的，因此可能对于选择性 septin 识别至关重要。这些非常规序列和结构特征产生亚稳态异质复合物，但其具有足够的特异性来促进正确的原丝组装。例如，缺乏超螺旋可能有助于解压并转变为反平行同二聚体状态。