BIOGRID CURATED DATA FOR PUBLICATION: A non-canonical mechanism for Crm1-export cargo complex assembly.

Protein-Protein, Genetic, and Chemical Interactions for Fischer U (2015):A non-canonical mechanism for Crm1-export cargo complex assembly. curated by BioGRID (https://thebiogrid.org); ABSTRACT: The transport receptor Crm1 mediates the export of diverse cargos containing leucine-rich nuclear export signals (NESs) through complex formation with RanGTP. To ensure efficient cargo release in the cytoplasm, NESs have evolved to display low affinity for Crm1. However, mechanisms that overcome low affinity to assemble Crm1-export complexes in the nucleus remain poorly understood. In this study, we reveal a new type of RanGTP-binding protein, Slx9, which facilitates Crm1 recruitment to the 40S pre-ribosome-associated NES-containing adaptor Rio2. In vitro, Slx9 binds Rio2 and RanGTP, forming a complex. This complex directly loads Crm1, unveiling a non-canonical stepwise mechanism to assemble a Crm1-export complex. A mutation in Slx9 that impairs Crm1-export complex assembly inhibits 40S pre-ribosome export. Thus, Slx9 functions as a scaffold to optimally present RanGTP and the NES to Crm1, therefore, triggering 40S pre-ribosome export. This mechanism could represent one solution to the paradox of weak binding events underlying rapid Crm1-mediated export.

蛋白质-蛋白质、遗传及化学相互作用数据集，源自Fischer U（2015年）的研究：《Crm1-输出货物复合体组装的非典型机制》。该数据集由BioGRID（https://thebiogrid.org）进行整理；摘要：转运受体Crm1通过与RanGTP形成复合物，介导含有富含亮氨酸的核输出信号（NESs）的多种货物输出。为确保在细胞质中高效释放货物，NESs已进化出对Crm1的低亲和力。然而，克服低亲和力以在细胞核中组装Crm1-输出复合体的机制仍鲜为人知。在本研究中，我们揭示了一种新型的RanGTP结合蛋白Slx9，该蛋白通过促进Crm1招募至与40S前核糖体相关联、含有NESs的适配器Rio2，从而发挥作用。体外实验中，Slx9与Rio2和RanGTP结合，形成复合物。此复合物直接装载Crm1，揭示了一种非典型、逐步组装Crm1-输出复合体的机制。Slx9中一个损害Crm1-输出复合体组装的突变，抑制了40S前核糖体的输出。因此，Slx9作为支架，最佳地呈现RanGTP和NESs至Crm1，从而触发40S前核糖体的输出。此机制可能代表解决Crm1介导的快速输出中弱结合事件悖论的一种策略。