Phosphate stabilization of intermolecular interactions
Phosphate stabilization of intermolecular interactions
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DOI：
10.1021/pr0503578
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发表时间：
2006-01-01
影响因子：
4.4
通讯作者：
Woods, AS
中科院分区：
文献类型：
--
作者：
Jackson, SN;Wang, HYJ;Woods, AS
受体异聚化是由两个受体上的表位相互作用引起的重要现象。已有研究表明多巴胺D-2-NMDA受体可能存在相互作用。我们认为，这种相互作用是通过NMDA NR 1亚基的酸性表位（KVNSEEEEDA）和D-2第三胞内环的碱性表位（VLRRRRKRVN）进行的，该表位也与腺苷A（2）A受体相互作用。在以前的工作中，我们强调了某些氨基酸残基的作用，主要是一个肽上的两个或更多个相邻的精氨酸和两个或更多个相邻的谷氨酸或天冬氨酸，或磷酸化残基在表位之间形成非共价复合物（NCX）。在目前的工作中，我们使用磷酸化（KVNSpEEEEEDA），非磷酸化（KVNSEEEEDA）和修饰（KVNpSAAAAAAA）形式的NMDA表位，可能与D-2表位相互作用，以研究气相稳定性的NCXs作为一个函数的标称能量给予NCX离子，因为它进入碰撞池。除了理论计算之外，实验数据用于计算每个静电复合物相对于KVNSpEEEEEDA的二聚体的稳定性。我们的研究结果表明磷酸基团在稳定分子相互作用中的重要性，并且与解离KVNpSEEEEDA二聚体离子所需的能量相比，需要明显更高的碰撞能量来完全解离通过静电相互作用形成的三种不同的NCX离子中的任何一种。这项研究强调了离子键的稳定性及其对蛋白质结构的重要性，因为它们在气相中的强大静电吸引力可以超过：共价键的强度。
Receptor heteromerization is an important phenomenon that results from the interaction of epitopes on two receptors. Previous studies have suggested the possibility of Dopamine D-2-NMDA receptors' interaction. We believe that the interaction is through an acidic epitope of the NMDA NR1 subunit (KVNSEEEEEDA) and a basic epitope of the D-2 third intracellular loop (VLRRRRKRVN), which was shown to also interact with the Adenosine A(2)A receptor. In previous work, we highlighted the role of certain amino acid residues, mainly two or more adjacent arginine on one peptide and two or more adjacent glutamate, or aspartate, or a phosphorylated residue on the other in the formation of noncovalent complexes (NCX) between epitopes. In the present work, we use the phosphorylated (KVNSpEEEEEDA), nonphosphorylated (KVNSEEEEEDA) and modified (KVNpSAAAAAAA) forms of the NMDA epitope that possibly interact with the D-2 epitope to investigate the gas-phase stability of the NCXs as a function of the nominal energy given to the NCX ion as it enters the collision cell. In addition to theoretical calculations, the experimental data was used to calculate the stability of each electrostatic complex versus that of the dimer of KVNSpEEEEEDA. Our results demonstrate the importance of the phosphate group in stabilizing molecular interactions and that appreciably higher collision energies are required to completely dissociate any of the three different NCX ions that are formed through electrostatic interaction in comparison to the energy required to dissociate the KVNpSEEEEEDA dimer ion, which is, mainly kept together by hydrogen bonding. This study emphasizes ionic bonds stability and their importance to protein structure as their potent electrostatic attractions can in the gas-phase surpass the :strength of covalent bonds.