Structural Studies of BPI, A Human LPS-Binding Protein

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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.