The Mon1-Ccz1 complex (MC1) is the guanine nucleotide exchange factor (GEF) for the Rab GTPase Ypt7/Rab7 and is required for endosomal maturation and fusion at the vacuole/lysosome. Here we present the overall architecture of MC1 from Chaetomium thermophilum, and in combining biochemical studies and mutational analysis in yeast, we identify the domains required for catalytic activity, complex assembly and localization of MC1. The crystal structure of a catalytic MC1 core complex bound to Ypt7 provides mechanistic insight into its function. We pinpoint the determinants that allow for a discrimination of the Rab7-like Ypt7 over the Rab5-like Vps21, which are both located on the same membrane. MC1 shares structural similarities with the TRAPP complex, but employs a novel mechanism to promote nucleotide exchange that utilizes a conserved lysine residue of Ypt7, which is inserted upon MC1 binding into the nucleotide-binding pocket of Ypt7 and contributes to specificity.

中文翻译：

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晚期内体Rab7样Ypt7鸟嘌呤核苷酸交换因子复合物Mon1-Ccz1的体系结构和机制。

Mon1-Ccz1复合物（MC1）是Rab GTPase Ypt7 / Rab7的鸟嘌呤核苷酸交换因子（GEF），是内体成熟和液泡/溶酶体融合所必需的。在这里，我们介绍了嗜热Chaetomium thermophilum MC1的总体架构，并结合了酵母中的生化研究和突变分析，我们确定了催化活性，MC1的复杂组装和定位所需的域。与Ypt7结合的催化MC1核心配合物的晶体结构提供了对其功能的机械洞察力。我们查明了决定因素，该决定因素允许区分Rab7样的Ypt7而不是Rab5样的Vps21，它们都位于同一膜上。MC1与TRAPP复合体具有相似的结构，