Role of Arg182 in the second extracellular loop of angiotensin II receptor AT2 in ligand binding.
Role of Arg182 in the second extracellular loop of angiotensin II receptor AT2 in ligand binding.
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Arg182 在血管紧张素 II 受体 AT2 的第二个细胞外环中在配体结合中的作用。
DOI：
10.1006/bbrc.1999.1405
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Pulakat,L
中科院分区：
文献类型：
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作者：
Kurfis,J;Knowle,D;Pulakat,L
Ang II中Tyr 4的酚侧链与AT 1受体的Arg 167侧链相互作用。为了确定类似的Arg 182对AT 2配体结合特性的贡献，我们用Glu和Ala取代Arg 182，并分析配体结合特性。我们的研究结果表明，用Glu或Ala取代Arg 182，可消除AT 2受体结合非特异性肽配体125 I-Ang II和[125 I-Sar 1-Ile 8]Ang II以及AT 2受体特异性肽配体125 I-CGP 42112 A的能力。我们先前已经证明，在第五TMD中用带负电荷的Glu侧链取代带正电荷的Lys 215侧链并不改变125 I-CGP 42112 A与AT 2受体的高亲和力结合。然而，Arg 182 Glu突变体的配体结合特性表明，位于第二ECL和第四TMD的交界处的Arg 182的带正电荷的侧链对于所有三种肽配体与AT 2受体的高亲和力结合是至关重要的。
The phenolic side chain of Tyr4present in Ang II is proposed to interact with the side chain of Arg 167 of the AT1 receptor. To determine the contribution of the analogous Arg182 in the ligand-binding properties of the AT2, we replaced the Arg182 with Glu and Ala, and analyzed the ligand-binding properties. Our results suggest that replacing Arg182 with either Glu or Ala abolished the ability of the AT2 receptor to bind the nonspecific peptidic ligands,125I-Ang II and [125I-Sar1-Ile8]Ang II, as well as the AT2 receptor-specific peptidic ligand125I-CGP42112A. We have shown previously that replacing the positively charged side chain of Lys215 with the negatively charged side chain of Glu in the fifth TMD did not alter the high affinity binding of125I-CGP42112A to the AT2 receptor. However, ligand-binding properties of the Arg182Glu mutant suggest that positively charged side chain of Arg182 located in the junction of second ECL and the fourth TMD is critical for high affinity binding of all three peptidic ligands to the AT2 receptor.