MUTATIONAL ANALYSIS OF THE HUMAN KDEL RECEPTOR - DISTINCT STRUCTURAL REQUIREMENTS FOR GOLGI RETENTION, LIGAND-BINDING AND RETROGRADE TRANSPORT
MUTATIONAL ANALYSIS OF THE HUMAN KDEL RECEPTOR - DISTINCT STRUCTURAL REQUIREMENTS FOR GOLGI RETENTION, LIGAND-BINDING AND RETROGRADE TRANSPORT
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DOI：
10.1002/j.1460-2075.1993.tb05943.x
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发表时间：
1993-07-01
期刊：
影响因子：
11.4
通讯作者：
PELHAM, HRB
中科院分区：
文献类型：
--
作者：
TOWNSLEY, FM;WILSON, DW;PELHAM, HRB
KDEL受体是一种七跨膜结构域蛋白，负责从高尔基复合体中回收内质网（ER）蛋白。它是高尔基体的临时居民：在结合含有KDEL的配体后，它移动到ER，在那里释放配体。我们在COS细胞中表达了人类受体的突变形式，并研究了它们的细胞内位置和配体结合能力。我们表明，配体结合依赖于跨膜结构域内的带电残基。令人惊讶的是，逆行转运占用受体是不受大多数突变的细胞质环，但严重依赖于天冬氨酸残基在第七跨膜结构域。保留在高尔基体中既不需要配体结合，也不需要这种天冬氨酸残基，因此不依赖于受体再循环。我们认为受体的运动是由膜双层内的构象变化和分子间相互作用控制的。
The KDEL receptor is a seven-transmembrane-domain protein that is responsible for the retrieval of endoplasmic reticulum (ER) proteins from the Golgi complex. It is a temporary resident of the Golgi apparatus: upon binding a KDEL-containing ligand, it moves to the ER, where the ligand is released. We have expressed mutant forms of the human receptor in COS cells and examined their intracellular locations and ligand-binding capacities. We show that ligand binding is dependent on charged residues within the transmembrane domains. Surprisingly, retrograde transport of occupied receptor is unaffected by most mutations in the cytoplasmic loops, but is critically dependent upon an aspartic acid residue in the seventh transmembrane domain. Retention in the Golgi apparatus requires neither ligand binding nor this aspartate residue, and thus is independent of receptor recycling. We suggest that movement of the receptor is controlled by conformational changes and intermolecular interactions within the membrane bilayer.