Pb2+作为蛋白质膜相互作用的调节器
Krystal A Morales1, Mauricio Lasagna, Alexey V Gribenko
1Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, USA.
Journal of the American Chemical Society
|May 28, 2011
概括
(Pb2+) 与蛋白激酶Cα (PKCα) 的C2α域结合的亲和力比 (Ca2+) 高,影响其膜结合,并可能导致毒性.
科学领域:
- 生物化学 生物化学
- 毒理学 毒理学 毒理学
- 结构生物学 结构生物学
背景情况:
- (Pb2+) 是一种环境毒素,它模仿了必不可少的双价金属离子.
- 导致毒性的分子机制尚未完全理解.
- 蛋白激酶Cα (PKCα) 是一种已知的的分子标.
研究的目的:
- 研究Pb2+对PKCα.的C2α域的结构和膜结合作用.
- 阐明Pb2+和C2α之间的分子相互作用.
主要方法:
- 核磁共振 (NMR) 光谱学 核磁共振 (NMR) 光谱学
- 异热定位热量计 (ITC) 是一种热量计.
- 在X射线晶体学.
- 佛斯特共振能量转移 (FRET) 光谱学
主要成果:
- C2α与Pb2+结合的亲和力比Ca2+更高.
- 晶体结构揭示Pb2+协调需要侧链旋转,与共存的全向和半向几何形状.
- Pb2+从C2α中取代Ca2+并竞争脂质双层上的膜结合位点.
结论:
- Pb2+与C2α的相互作用与Ca2+显著不同.
- Pb2+与C2α的结合及其对膜部位的竞争可能导致PKCα抑制和毒性.
相关概念视频
Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Multi-pass Transmembrane Proteins and β-barrels
In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...
IP3/DAG Signaling Pathway
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Phosphoinositides and PIPs
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
Amplifying Signals via Second Messengers
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...


