Structural Studies of BPI, A Human LPS-Binding Protein

脂多糖（lipopolaccharides， LPS）是在革兰氏阴性菌外膜中发现的复杂的糖脂，在高等生物中可引起多种生物反应。人杀菌剂/通透性增加蛋白（BPI）与LPS具有高亲和力，并能在体内调节其生物活性。最近用两种结合的磷脂对BPI晶体结构的测定为进一步表征该蛋白提供了框架。x射线衍射和其他生物物理技术将用于研究结合磷脂对BPI结构和稳定性的影响。此外，BPI与LPS或LPS类似物片段的新型配合物将通过动态光散射和x射线晶体学表征。这些实验将提供蛋白质-LPS相互作用的分子基础上的重要结构细节，以及蛋白质调节LPS生物活性的能力。许多普通细菌的外表面都有一种叫做脂多糖（LPS）的分子。因为只有细菌而没有其他生物产生LPS，它作为细菌附近的信号。人类和许多动物体内都有一种蛋白质，可以在体内检测到微量的脂多糖。其中之一是BPI，一种杀菌/增加渗透性的蛋白质。BPI在许多相似分子中识别细菌LPS并与之紧密结合。几种实验技术，包括x射线衍射，将用于检查在LPS存在下BPI的分子结构。通过研究BPI如何与LPS相互作用，将了解蛋白质如何检测LPS以及LPS如何在生物有机体中触发许多不同的反应。

Beamer, LisaMCB-9974912Lipopolysaccharides (LPS) are complex glycolipids found in the outer membrane of Gram-negative bacteria that can elicit diverse biological responses in higher organisms. The human bactericidal/permeability-increasing protein (BPI) binds to LPS with high affinity and can modulate its biological activity in vivo. The recent determination of the crystal structure of BPI with two bound phospholipids provides a framework for further characterization of the protein. X-ray diffraction and other biophysical techniques will be used to investigate the effects of the bound phospholipids on BPI's structure and stability. In addition, novel complexes of BPI with fragments of LPS or LPS analogs will be characterized by dynamic light scattering and X-ray crystallography. These experiments will provide important structural details on the molecular basis of protein-LPS interactions, and the ability of proteins to modulate the bioactivity of LPS. Many common bacteria have a molecule called lipopolysaccharide (LPS) on their outer surface. Because only bacteria and no other organisms make LPS, it acts as a signal that bacteria are near. Humans and many animals have proteins that can detect tiny amounts of LPS when it is found in the body. One of these is BPI, the bactericidal/permeability-increasing protein. BPI recognizes bacterial LPS in the midst of many similar molecules and binds to it very tightly. Several experimental techniques, including X-ray diffraction, will be used to examine the molecular structure of BPI in the presence of LPS. By studying how BPI interacts with LPS, much will be learned about how proteins detect LPS and how LPS can trigger many different responses in biological organisms.