ISOLATION OF THE MITOCHONDRIAL BENZODIAZEPINE RECEPTOR - ASSOCIATION WITH THE VOLTAGE-DEPENDENT ANION CHANNEL AND THE ADENINE-NUCLEOTIDE CARRIER
ISOLATION OF THE MITOCHONDRIAL BENZODIAZEPINE RECEPTOR - ASSOCIATION WITH THE VOLTAGE-DEPENDENT ANION CHANNEL AND THE ADENINE-NUCLEOTIDE CARRIER
复制标题
DOI：
10.1073/pnas.89.8.3170
复制
发表时间：
1992-04-15
影响因子：
11.1
通讯作者：
SNYDER, SH
中科院分区：
文献类型：
--
作者：
MCENERY, MW;SNOWMAN, AM;SNYDER, SH
线粒体苯二氮卓类受体（mBzR）已溶解保留可逆的配体结合，和相关的亚基进行了表征。mBzR包含18-、30-和32-kDa的免疫学上不同的蛋白质亚基。18-kDa蛋白质由异喹啉甲酰胺mBzR配体[H-3] PK 14105标记，而30-和32-kDa亚基由苯二氮卓类（Bz）配体[H-3]氟硝西泮和[H-3]AHN-086标记。选择性抗体和试剂将32和30 kDa蛋白分别鉴定为电压依赖性阴离子通道（VDAC）和腺嘌呤核苷酸载体（ADC）。虽然异喹啉甲酰胺和Bz配体靶向不同的亚基，但它们以变构方式相互作用，因为Bz和异喹啉甲酰胺配体的结合在低纳摩尔浓度下是相互竞争的。此外，曙红-5-马来酰亚胺和氯化汞通过ADC中存在的巯基抑制[H-3] PK 11195与完整受体的结合。VDAC和ADC，外和内线粒体膜通道蛋白，分别与18 kDa的亚基，可能包括在功能上重要的转运位点在两个线粒体膜的交界处的mBzR。
The mitochondrial benzodiazepine receptor (mBzR) has been solubilized with retention of reversible ligand binding, and the associated subunits were characterized. mBzR comprises immunologically distinct protein subunits of 18-, 30-, and 32-kDa. The 18-kDa protein is labeled by the isoquinoline carboxamide mBzR ligand [H-3]PK14105, whereas the 30- and 32-kDa subunits are labeled by the benzodiazepine (Bz) ligands [H-3]flunitrazepam and [H-3]AHN-086. Selective antibodies and reagents identify the 32- and 30-kDa proteins as the voltage-dependent anion channel (VDAC) and the adenine nucleotide carrier (ADC), respectively. While isoquinoline carboxamide and Bz ligands target different subunits, they interact allosterically, as the binding of Bz and isoquinoline carboxamide ligands is mutually competitive at low nanomolar concentrations. Moreover, eosin-5-maleimide and mercuric chloride inhibit [H-3]PK11195 binding to the intact receptor via sulfhydryl groups that are present in ADC. VDAC and ADC, outer and inner mitochondrial membrane channel proteins, respectively, together with the 18-kDa subunit, may comprise mBzR at functionally important transport sites at the junction of two mitochondrial membranes.