The beta subunit of the signal recognition particle receptor is a transmembrane GTPase that anchors the alpha subunit, a peripheral membrane GTPase, to the endoplasmic reticulum membrane.
The beta subunit of the signal recognition particle receptor is a transmembrane GTPase that anchors the alpha subunit, a peripheral membrane GTPase, to the endoplasmic reticulum membrane.
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DOI：
10.1083/jcb.128.3.273
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发表时间：
1995-02
期刊：
影响因子：
--
通讯作者：
Walter P
中科院分区：
文献类型：
--
作者：
Miller JD;Tajima S;Lauffer L;Walter P
信号识别颗粒受体 (SR) 是分泌蛋白和膜蛋白共翻译靶向内质网 (ER) 膜所必需的。在靶向过程中，SR 与信号识别颗粒 (SRP) 相互作用，信号识别颗粒与新生蛋白链的信号序列结合。这种相互作用催化新生链从 SRP 到 ER 膜中的蛋白质易位装置的 GTP 依赖性转移。 SR 是一种异二聚体蛋白，由 69 kD 亚基 (SR α) 和 30 kD 亚基 (SR β) 组成，它们以未知方式与 ER 膜相关。 SR α 和 SRP (SRP54) 的 54 kD 亚基均包含 SR 和 SRP 功能所需的相关 GTPase 结构域。编码 SR beta 的 cDNA 的分子克隆和测序表明，SR beta 是一种跨膜蛋白，与 SR alpha 和 SRP54 一样，是 GTPase 超家族的成员。尽管 SR beta 定义了自己的 GTPase 亚家族，但它与 ARF 和 Sar1 关系较远。使用 UV 交联，我们确认 SR beta 特异性结合 GTP。蛋白水解消化实验表明，SR α 是 SRP 与 SR 相互作用所必需的。 SR α 似乎与 ER 膜外周相关，我们认为 SR β 作为一种完整的膜蛋白，介导 SR α 的膜关联。然而，其鸟嘌呤核苷酸结合域的发现使得其作用可能比 SR α 的被动锚定更加复杂。这些发现表明，三种直接相互作用的 GTPases 的级联在蛋白质靶向内质网膜的过程中发挥作用。
The signal recognition particle receptor (SR) is required for the cotranslational targeting of both secretory and membrane proteins to the endoplasmic reticulum (ER) membrane. During targeting, the SR interacts with the signal recognition particle (SRP) which is bound to the signal sequence of the nascent protein chain. This interaction catalyzes the GTP-dependent transfer of the nascent chain from SRP to the protein translocation apparatus in the ER membrane. The SR is a heterodimeric protein comprised of a 69-kD subunit (SR alpha) and a 30- kD subunit (SR beta) which are associated with the ER membrane in an unknown manner. SR alpha and the 54-kD subunits of SRP (SRP54) each contain related GTPase domains which are required for SR and SRP function. Molecular cloning and sequencing of a cDNA encoding SR beta revealed that SR beta is a transmembrane protein and, like SR alpha and SRP54, is a member of the GTPase superfamily. Although SR beta defines its own GTPase subfamily, it is distantly related to ARF and Sar1. Using UV cross-linking, we confirm that SR beta binds GTP specifically. Proteolytic digestion experiments show that SR alpha is required for the interaction of SRP with SR. SR alpha appears to be peripherally associated with the ER membrane, and we suggest that SR beta, as an integral membrane protein, mediates the membrane association of SR alpha. The discovery of its guanine nucleotide-binding domain, however, makes it likely that its role is more complex than that of a passive anchor for SR alpha. These findings suggest that a cascade of three directly interacting GTPases functions during protein targeting to the ER membrane.