Crystal structure of the phosphatidylethanolamine-binding protein from bovine brain: a novel structural class of phospholipid-binding proteins

Abstract

This study shows that PEBP is not related to the G-protein family nor to known lipid-binding proteins, and therefore defines a novel structural family of phospholipid-binding proteins. The PEBP structure contains no internal hydrophobic pocket, as described for lipocalins or small phospholipid-transfer proteins. Nevertheless, in PEBP, a small cavity close to the protein surface has a high affinity for anions, such as phosphate and acetate, and also phosphorylethanolamine. We suggest that this cavity corresponds to the binding site of the polar head group of phosphatidylethanolamine.

A Novel Human Phosphatidylethanolamine-binding Protein Resists Tumor Necrosis Factor α-induced Apoptosis by Inhibiting Mitogen-activated Protein Kinase Pathway Activation and Phosphatidylethanolamine Externalization

“…Sequence analysis and preliminary homology modeling based on the crystal structure of bovine and human PEBPs (26,32) suggest that hPEBP4 also contains a putative PE-binding pocket, which could potentially allow anchoring of this protein to the inner leaflet of membranes. In addition, hPEBP4 has high sequence and predicted topology homology with analogous Raf-1-and MEK-binding regions predicted in deletion studies (9).…”

“…Residues previously demonstrated to be conserved between all members of the family (Pro 97 , Asp 98 , Pro 100 , His 112 , and Arg 149 ) were also found in hPEBP4. These residues are thought to be involved in determining the local structure of a biologically important ligand-binding site in PEBPs (26). The two main regions of high sequence conservation among hPEBP4 and other PEBPs occurred between residues 91-117 and residues 141-153 (based on hPEBP4 numbering).…”

Raf Kinase Inhibitor Protein (RKIP) Dimer Formation Controls Its Target Switch from Raf1 to G Protein-coupled Receptor Kinase (GRK) 2

“…Surprisingly, homo-oligomerization as an efficient mechanism to control protein-protein interactions has thus far not been taken into consideration for RKIP. Although putative dimers and higher-order oligomers of RKIP have been observed by Bollengier et al (44) in human brain lysates and in crystal structures of human RKIP, a bacterial and a plant homolog of RKIP (8,15,19), the existence or physiological implications of RKIP dimers or oligomers in mammalian cells have not been investigated under physiological conditions.…”

“…As controls, we used either mock-transfected cells or cells transfected with N-terminal RKIP fragments, which did not contain the loop sequence (supplemental Fig. S4, A (RKIP [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] ) and C (RKIP )). In accordance with our previous results, prevention of RKIP dimerization by loop 127-150 was accompanied by inhibition of PKC-induced RKIP-GRK2 assembly (Fig.…”

Heterologous Production of Fungal Maleidrides Reveals the Cryptic Cyclization Involved in their Biosynthesis

“…Other known maleidride producers appear to have pathways that only involve one class of dimerization, although it is possible that reinvestigation of the metabolites produced may identify other minor compounds with different dimerization modes. The PEBP‐like enzymes also appear to be involved in the dimerization, and although their catalytic role is not yet clear, it is possible their known anionic binding ability may be involved 27. One possibility may be the chaperoning of highly unstable carboxylates such as 10 in order to prevent premature decarboxylation prior to dimerization.…”