The mammalian Rab family of small GTPases: Definition of family and subfamily sequence motifs suggests a mechanism for functional specificity in the Ras superfamily
The mammalian Rab family of small GTPases: Definition of family and subfamily sequence motifs suggests a mechanism for functional specificity in the Ras superfamily
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DOI：
10.1006/jmbi.2000.4010
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发表时间：
2000-08-25
影响因子：
5.6
通讯作者：
Seabra, MC
中科院分区：
文献类型：
--
作者：
Pereira-Leal, JB;Seabra, MC
Rab/Ypt/Sec4 家族构成 GTPases Ras 超家族的最大分支，充当囊泡转运途径的重要调节因子。我们利用数据库中的大量信息来分析哺乳动物拉布家族。我们定义了 Rab 保守序列，使用保守的 PM 和 G 基序作为“地标”，指定 Rab 家族 (RabF) 基序。 Rab 特异性区域用于识别数据库中的新 Rab 蛋白并提出命名规则。令人惊讶的是，我们发现 RabF 区域聚集在开关 I 和开关 II 区域内及其周围，即在 GDP 或 GTP 结合时改变构象的区域。这一发现表明 Rab 效应子相互作用的特异性不能像通常推断的那样仅通过开关区域来赋予。相反，我们提出了一种模型，通过该模型，效应器结合到 RabF（开关）区域以区分核苷酸结合状态，同时结合到赋予相互作用特异性的其他区域，可能是我们在这里定义的 Rab 亚家族 (RabSF) 特定区域。我们讨论支持该模型的结构和功能数据及其对 Ras 蛋白质超家族的普遍适用性。 (C) 2000 年学术出版社。
The Rab/Ypt/Sec4 family forms the largest branch of the Ras superfamily of GTPases, acting as essential regulators of vesicular transport pathways. We used the large amount of information in the databases to analyse the mammalian Rab family. We defined Rab-conserved sequences that we designate Rab family (RabF) motifs using the conserved PM and G motifs as "landmarks". The Rab-specific regions were used to identify new Rab proteins in the databases and suggest rules for nomenclature. Surprisingly, we find that RabF regions cluster in and around switch I and switch II regions, i.e. the regions that change conformation upon GDP or GTP binding. This finding suggests that specificity of Rab-effector interaction cannot be conferred solely through the switch regions as is usually inferred. Instead, we propose a model whereby an effector binds to RabF (switch) regions to discriminate between nucleotide-bound states and simultaneously to other regions that confer specificity to the interaction, possibly Rab subfamily (RabSF) specific regions that we also define here. We discuss structural and functional data that support this model and its general applicability to the Ras superfamily of proteins. (C) 2000 Academic Press.