Structures of cGMP-Dependent Protein Kinase (PKG) Iα Leucine Zippers Reveal an Interchain Disulfide Bond Important for Dimer Stability.
Structures of cGMP-Dependent Protein Kinase (PKG) Iα Leucine Zippers Reveal an Interchain Disulfide Bond Important for Dimer Stability.
复制标题
cGMP 依赖性蛋白激酶 (PKG) Iα 亮氨酸拉链的结构揭示了对二聚体稳定性很重要的链间二硫键。
DOI：
10.1021/acs.biochem.5b00572
复制
发表时间：
2015
期刊：
影响因子：
2.9
通讯作者：
Kim,Choel
中科院分区：
文献类型：
--
作者：
Qin,Liying;Reger,AlbertS;Guo,Elaine;Yang,MatthewP;Zwart,Peter;Casteel,DarrenE;Kim,Choel
cGMP依赖性蛋白激酶（PKG）Iα是平滑肌张力和血管舒张的中枢调节因子。N-末端亮氨酸拉链（LZ）结构域通过与G-激酶锚定蛋白相互作用二聚化并靶向PKG Iα。PKG Iα LZ含有C42，已知其在氧化时形成二硫键并激活PKG Iα。为了了解PKG Iα LZ和C42-C42′二硫键的分子细节，我们确定了PKG Iα野生型（WT）LZ和C42 L LZ的晶体结构。我们的数据表明，C42-C42′二硫键显著稳定PKG Iα，C42 L突变体在结构上模拟氧化的WT LZ。
cGMP-dependent protein kinase (PKG) Iα is a central regulator of smooth muscle tone and vasorelaxation. The N-terminal leucine zipper (LZ) domain dimerizes and targets PKG Iα by interacting with G-kinase-anchoring proteins. The PKG Iα LZ contains C42 that is known to form a disulfide bond upon oxidation and to activate PKG Iα. To understand the molecular details of the PKG Iα LZ and C42–C42′ disulfide bond, we determined crystal structures of the PKG Iα wild-type (WT) LZ and C42L LZ. Our data demonstrate that the C42–C42′ disulfide bond dramatically stabilizes PKG Iα and that the C42L mutant mimics the oxidized WT LZ structurally.