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:

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]

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.

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.

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.

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.

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.

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.

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.

Examples:

TC#NameOrganismal TypeExample
1.C.40.1.1

Bacterial permeability inducing protein, BPIP precursor, of 487 aas and 1 N-terminal TMS. 

Animals

BPIP precursor of Homo sapiens

 
1.C.40.1.2LBP (lipopolysaccharide binding protein) precursor Animals LBP precursor of Homo sapiens
 
1.C.40.1.3CETP (cholesterylester transfer protein) precursor Animals CETP precursor of Oryctolagus cuniculus
 
1.C.40.1.4Phospholipid transfer protein (PLTP) precursor (lipid transfer protein II)AnimalsPLTP of Homo sapiens (493 aas; P55058)
 
1.C.40.1.5

NRF5 protein of 551 aas.  Plays a role in the uptake of a range of molecules including phosphatidylserine, lipids and xenobiotic compounds from the intestine to surrounding tissues (Choy and Thomas 1999). Possesses lipid transfer activity and mediates transport of lipids from theintestine to the reproductive tract. Binds phosphatidylserine and plays a role in the efficient clearance of cell corpses by mediating phosphatidylserine appearance on phagocytic cells, thus promoting phagocytic engulfment of apoptotic cells (Zhang et al. 2012). Vital for embryonic development.  Gene deletion leads to extension of the life span (Brejning et al. 2014).

Animals

NRF5 of Caenorhabditis elegans

 
1.C.40.1.6

BPI-like protein of 458 aas and 2 TMSs.

BPI-like protein of Homo sapiens

 
1.C.40.1.7
Bactericidal/permeability-increasing protein, BPI of 472 aas and 2 TMSs.

BPI of Larimichthys crocea (Large yellow croaker) (Pseudosciaena crocea)

 
1.C.40.1.8

Cholesteryl ester transfer protein, CETP of 493 aas and 1 TMS.  Involved in the transfer of neutral lipids, including cholesteryl esters and triglycerides, among lipoprotein particles. Allows the net movement of cholesteryl esters from high density lipoproteins/HDL to triglyceride-rich very low density lipoproteins/VLDL, and the equimolar transport of triglyceride from VLDL to HDL (Drayna et al. 1987; Morton and Izem 2014). Regulates reverse cholesterol transport, by which excess cholesterol is removed from peripheral tissues and returned to the liver for elimination (Qiu et al. 2007).

CETP of Homo sapiens

 
Examples:

TC#NameOrganismal TypeExample
1.C.40.2.1

Takeout-like protein-1, To1, of 240 aas and 1 N-terminal TMS.  Takeout proteins are insect juvenile hormone-binding proteins and arthropod allergens, which transport lipid hormones to target tissues during insect development (Alva and Lupas 2016).

To1 of Epiphyas postvittana (Light brown apple moth)

 
1.C.40.2.2

Takeout-like protein, To3 of 261 aas and 1 N-terminal TMS

To3 of Danaus plexippus (Monarch butterfly)