Pang Andrew, Arinaminpathy Yalini, Sansom Mark S P, Biggin Philip C
Laboratory of Molecular Biophysics, Department of Biochemistry, The University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
FEBS Lett. 2003 Aug 28;550(1-3):168-74. doi: 10.1016/s0014-5793(03)00866-4.
Periplasmic binding proteins from Gram-negative bacteria possess a common architecture, comprised of two domains linked by a hinge region, a fold which they share with the neurotransmitter-binding domains of ionotropic glutamate receptors (GluRs). Glutamine-binding protein (GlnBP) is one such protein, whose crystal structure has been solved in both open and closed forms. Multi-nanosecond molecular dynamics simulations have been used to explore motions about the hinge region and how they are altered by ligand binding. Glutamine binding is seen to significantly reduce inter-domain motions about the hinge region. Essential dynamics analysis of inter-domain motion revealed the presence of both hinge-bending and twisting motions, as has been reported for a related sugar-binding protein. Significantly, the influence of the ligand on GlnBP dynamics is similar to that previously observed in simulations of rat glutamate receptor (GluR2) ligand-binding domain. The essential dynamics analysis of GlnBP also revealed a third class of motion which suggests a mechanism for signal transmission in GluRs.
革兰氏阴性菌的周质结合蛋白具有共同的结构，由通过铰链区连接的两个结构域组成，这种折叠结构与离子型谷氨酸受体（GluRs）的神经递质结合结构域相同。谷氨酰胺结合蛋白（GlnBP）就是这样一种蛋白，其晶体结构已通过开放和闭合两种形式解析出来。多纳秒级的分子动力学模拟已被用于探索围绕铰链区的运动以及它们如何因配体结合而改变。可以看到谷氨酰胺结合会显著减少围绕铰链区的结构域间运动。对结构域间运动的主成分动力学分析揭示了铰链弯曲和扭转运动的存在，这与之前报道的一种相关糖结合蛋白的情况相同。值得注意的是，配体对GlnBP动力学的影响与之前在大鼠谷氨酸受体（GluR2）配体结合结构域模拟中观察到的相似。对GlnBP的主成分动力学分析还揭示了第三类运动，这表明了GluRs信号传递的一种机制。
