营养信号、膜运输和神经退行性病变中的 Longin 结构域 GAP 复合物。
Longin domain GAP complexes in nutrient signalling, membrane traffic and neurodegeneration.
机构信息
Department of Molecular and Cell Biology, University of California Berkeley, CA, USA.
California Institute for Quantitative Biosciences, University of California, Berkeley, CA, USA.
出版信息
FEBS Lett. 2023 Mar;597(6):750-761. doi: 10.1002/1873-3468.14538. Epub 2022 Nov 22.
Small GTPases act as molecular switches and control numerous cellular processes by their binding and hydrolysis of guanosine triphosphate (GTP). The activity of small GTPases is coordinated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). Recent structural and functional studies have characterized a subset of GAPs whose catalytic units consist of longin domains. Longin domain containing GAPs regulate small GTPases that facilitate nutrient signalling, autophagy, vesicular trafficking and lysosome homeostasis. All known examples in this GAP family function as part of larger multiprotein complexes. The three characterized mammalian protein complexes in this class are FLCN:FNIP, GATOR1 and C9orf72:SMCR8. Each complex carries out a unique cellular function by regulating distinct small GTPases. In this article, we explore the roles of longin domain GAPs in nutrient sensing, membrane dynamic, vesicular trafficking and disease. Through a structural lens, we examine the mechanism of each longin domain GAP and highlight potential therapeutic applications.
小分子 GTP 酶作为分子开关，通过结合和水解鸟苷三磷酸（GTP）来控制众多细胞过程。小分子 GTP 酶的活性由鸟嘌呤核苷酸交换因子（GEF）和 GTP 酶激活蛋白（GAP）协调。最近的结构和功能研究已经确定了一小部分 GAP，其催化单元由 longin 结构域组成。含 longin 结构域的 GAP 调节有助于营养信号转导、自噬、囊泡运输和溶酶体动态平衡的小分子 GTP 酶。该 GAP 家族中的所有已知成员均作为更大的多蛋白复合物的一部分发挥作用。该类别中三个已鉴定的哺乳动物蛋白复合物是 FLCN：FNIP、GATOR1 和 C9orf72：SMCR8。每个复合物通过调节不同的小分子 GTP 酶来执行独特的细胞功能。在本文中，我们探讨了 longin 结构域 GAP 在营养感应、膜动态、囊泡运输和疾病中的作用。通过结构视角，我们研究了每个 longin 结构域 GAP 的机制，并强调了潜在的治疗应用。
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