The assembly of a septin filament requires that homologous monomers must distinguish between one another in establishing appropriate interfaces with their neighbors. To understand this phenomenon at the molecular level, we present the first four crystal structures of heterodimeric septin complexes. We describe in detail the two distinct types of G-interface present within the octameric particles, which must polymerize to form filaments. These are formed between SEPT2 and SEPT6 and between SEPT7 and SEPT3, and their description permits an understanding of the structural basis for the selectivity necessary for correct filament assembly. By replacing SEPT6 by SEPT8 or SEPT11, it is possible to rationalize Kinoshita's postulate, which predicts the exchangeability of septins from within a subgroup. Switches I and II, which in classical small GTPases provide a mechanism for nucleotide-dependent conformational change, have been repurposed in septins to play a fundamental role in molecular recognition. Specifically, it is switch I which holds the key to discriminating between the two different G-interfaces. Moreover, residues which are characteristic for a given subgroup play subtle, but pivotal, roles in guaranteeing that the correct interfaces are formed.

隔膜蛋白丝的组装要求同源单体在与邻居建立适当的界面时必须彼此区分。为了在分子水平上理解这一现象，我们介绍了异二聚体Septin复合物的前四个晶体结构。我们详细描述了八聚体颗粒中存在的两种不同类型的G界面，它们必须聚合形成长丝。它们形成在SEPT2和SEPT6之间以及SEPT7和SEPT3之间，其描述允许理解正确的灯丝组件所必需的选择性的结构基础。通过将SEPT6替换为SEPT8或SEPT11，可以合理化Kinoshita的假设，可以预测亚组内Septin的可交换性。开关I和II在经典的小GTP酶中提供了核苷酸依赖性构象变化的机制，已被重新用于Septin中，以在分子识别中发挥重要作用。具体来说，是开关I拥有区分两个不同G接口的关键。此外，给定亚组的特征残基在确保形成正确的界面方面起着微妙而关键的作用。