Septin family proteins are quite similar to each other both within and between eukaryotic species. Typically, multiple discrete septins co‐assemble into linear heterooligomers (usually hexameric or octameric rods) with a variety of cellular functions. We know little about how incorporation of different septins confers different properties to such complexes. This issue is especially acute in human cells where 13 separate septin gene products (often produced in multiple forms arising from alternative start codons and differential splicing) are expressed in a tissue‐specific manner. Based on sequence alignments and phylogenetic criteria, human septins fall into four distinct groups predictive of their interactions, that is, members of the same group appear to occupy the same position within oligomeric septin protomers, which are “palindromic” (have twofold rotational symmetry about a central homodimeric pair). Many such protomers are capable of end‐to‐end polymerization, generating filaments. Over a decade ago, a study using X‐ray crystallography and single‐particle electron microscopy deduced the arrangement within recombinant heterohexamers comprising representatives of three human septin groups—SEPT2, SEPT6, and SEPT7. This model greatly influenced subsequent studies of human and other septin complexes, including how incorporating a septin from a fourth group forms heterooctamers, as first observed in budding yeast. Two recent studies, including one in this issue of Cytoskeleton, provide clear evidence that, in fact, the organization of subunits within human septin heterohexamers and heterooctamers is inverted relative to the original model. These findings are discussed here in a broader context, including possible causes for the initial confusion.

中文翻译：

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彻底翻转：人类败血症蛋白异寡聚体的组织。

Septin家族蛋白在真核物种内部和之间都非常相似。通常，多个离散的脓蛋白共同组装成具有多种细胞功能的线性异低聚物（通常是六聚体或八聚体棒）。我们对不同脓蛋白的掺入如何赋予此类复合物不同的特性知之甚少。这个问题在人类细胞中尤其严重，其中 13 个独立的 septin 基因产物（通常由替代起始密码子和差异剪接产生多种形式）以组织特异性方式表达。根据序列比对和系统发育标准，人类脓毒蛋白分为四个不同的组，可预测它们的相互作用，也就是说，同一组的成员似乎在寡聚脓毒蛋白原聚体中占据相同的位置，这些原聚体是“回文的”（关于中心同二聚体对）。许多这样的原聚体能够进行端对端聚合，产生细丝。十多年前，一项使用 X 射线晶体学和单粒子电子显微镜的研究推断出重组异六聚体中的排列，该重组异六聚体包含三个人类脓毒症组的代表——SEPT2、SEPT6 和 SEPT7。该模型极大地影响了人类和其他败血症蛋白复合物的后续研究，包括如何合并来自第四组的败血症蛋白形成异八聚体，正如首次在芽殖酵母中观察到的那样。最近的两项研究，包括本期《细胞骨架》中的一项研究，提供了明确的证据，表明事实上，人脓毒症异六聚体和异八聚体内的亚基组织相对于原始模型是相反的。这里在更广泛的背景下讨论这些发现，包括最初混乱的可能原因。