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1.C.40 The Bactericidal Permeability-Increasing Protein (BPIP) Family

The BPI protein is produced within the granules of neutrophiles (polymorphonuclear leukocytes) of mammals. They have bacteriocidal activity against many species of Gram-negative bacteria. The cationic N-terminal half of the protein has high affinity for the anionic LPS-containing outer membranes of these bacteria. BPIP can neutralize the toxic effects of LPS in humans.

The structure of BPIP's reveals a novel protein fold with two similar domains that give the protein two-fold symmetry. Two phospholipids are bound in a polar pocket of the protein.

While BPIP and lipopolysaccharide binding protein (LBP) are concerned with host responses to bacterial infections and LPS, respectively, other homologues such as CETP and PLTP (see below) and other lipid transport proteins regulate the sizes of LDL and HDL in the plasma of mammals. This family is called the BPI/LBP by SwissProt.

References associated with 1.C.40 family:

Alva, V. and A.N. Lupas. (2016). The TULIP superfamily of eukaryotic lipid-binding proteins as a mediator of lipid sensing and transport. Biochim. Biophys. Acta. [Epub: Ahead of Print] 26825693
Beamer, L.J., S.F. Carroll and D. Eisenberg (1997). Crystal structure of human BPI and two bound phospholipids at 2.4Å resolution. Science 276: 1861-1864. 9188532
Brejning, J., S. Nørgaard, L. Schøler, T.H. Morthorst, H. Jakobsen, G.J. Lithgow, L.T. Jensen, and A. Olsen. (2014). Loss of NDG-4 extends lifespan and stress resistance in Caenorhabditis elegans. Aging Cell 13: 156-164. 24286221
Choy, R.K. and J.H. Thomas. (1999). Fluoxetine-resistant mutants in C. elegans define a novel family of transmembrane proteins. Mol. Cell 4: 143-152. 10488330
Drayna, D., A.S. Jarnagin, J. McLean, W. Henzel, W. Kohr, C. Fielding, and R. Lawn. (1987). Cloning and sequencing of human cholesteryl ester transfer protein cDNA. Nature 327: 632-634. 3600759
Morton, R.E. and L. Izem. (2014). Cholesteryl ester transfer proteins from different species do not have equivalent activities. J Lipid Res 55: 258-265. 24293641
Qiu, X., A. Mistry, M.J. Ammirati, B.A. Chrunyk, R.W. Clark, Y. Cong, J.S. Culp, D.E. Danley, T.B. Freeman, K.F. Geoghegan, M.C. Griffor, S.J. Hawrylik, C.M. Hayward, P. Hensley, L.R. Hoth, G.A. Karam, M.E. Lira, D.B. Lloyd, K.M. McGrath, K.J. Stutzman-Engwall, A.K. Subashi, T.A. Subashi, J.F. Thompson, I.K. Wang, H. Zhao, and A.P. Seddon. (2007). Crystal structure of cholesteryl ester transfer protein reveals a long tunnel and four bound lipid molecules. Nat Struct Mol Biol 14: 106-113. 17237796
Zhang, Y., H. Wang, E. Kage-Nakadai, S. Mitani, and X. Wang. (2012). C. elegans secreted lipid-binding protein NRF-5 mediates PS appearance on phagocytes for cell corpse engulfment. Curr. Biol. 22: 1276-1284. 22727700