PDBsum entry 1bd9

Lipid binding protein

PDB id: 1bd9

Contents

Protein chain

180 a.a. *

Waters ×394

* Residue conservation analysis

PDB id:

1bd9

Name:

Lipid binding protein

Title:

Human phosphatidylethanolamine binding protein

Structure:

Phosphatidylethanolamine binding protein. Chain: a, b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: cytoplasm, membrane-associated. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Biol. unit:

Dimer (from PQS)

Resolution:

2.05Å R-factor: 0.171 R-free: 0.232

Authors:

M.J.Banfield,J.J.Barker,A.C.F.Perry,R.L.Brady

Key ref:

M.J.Banfield et al. (1998). Function from structure? The crystal structure of human phosphatidylethanolamine-binding protein suggests a role in membrane signal transduction. Structure, 6, 1245-1254. PubMed id: 9782050 DOI: 10.1016/S0969-2126(98)00125-7

Date:

12-May-98 Release date: 16-Sep-98

Protein chains

P30086  (PEBP1_HUMAN) -  Phosphatidylethanolamine-binding protein 1 from Homo sapiens

Seq: 187 a.a.

Struc: 180 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/S0969-2126(98)00125-7

Structure 6:1245-1254 (1998)

PubMed id: 9782050

Function from structure? The crystal structure of human phosphatidylethanolamine-binding protein suggests a role in membrane signal transduction.

M.J.Banfield, J.J.Barker, A.C.Perry, R.L.Brady.

ABSTRACT

BACKGROUND: Proteins belonging to the phosphatidylethanolamine-binding protein (PEBP) family are highly conserved throughout nature and have no significant sequence homology with other proteins of known structure or function. A variety of biological roles have previously been described for members of this family, including lipid binding, roles as odorant effector molecules or opioids, interaction with the cell-signalling machinery, regulation of flowering plant stem architecture, and a function as a precursor protein of a bioactive brain neuropeptide. To date, no experimentally derived structural information has been available for this protein family. In this study we have used X-ray crystallography to determine the three-dimensional structure of human PEBP (hPEBP), in an attempt to clarify the biological role of this unique protein family. RESULTS: The crystal structures of two forms of hPEBP have been determined: one in the native state (at 2.05 A resolution) and one in complex with cacodylate (at 1.75 A resolution). The crystal structures reveal that hPEBP adopts a novel protein topology, dominated by the presence of a large central beta sheet, and is expected to represent the archaetypal fold for this family of proteins. Two potential functional sites have been identified from the structure: a putative ligand-binding site and a coupled cleavage site. hPEBP forms a dimer in the crystal with a distinctive dipole moment that may orient the oligomer for membrane binding. CONCLUSIONS: The crystal structure of hPEBP suggests that the ligand-binding site could accommodate the phosphate head groups of membrane lipids, therefore allowing the protein to adhere to the inner leaf of bilipid membranes where it would be ideally positioned to relay signals from the membrane to the cytoplasm. The structure also suggests that ligand binding may lead to coordinated release of the N-terminal region of the protein to form the hippocampal neurostimulatory peptide, which is known to be active in the development of the hippocampus. These studies are consistent with a primary biological role for hPEBP as a transducer of signals from the interior membrane surface.

Selected figure(s)

Figure 3.
Figure 3. Secondary structure elements in hPEBP. (a) The putative dimer of hPEBP formed by the two molecules in the asymmetric unit of the crystal. Also shown (arrow) is the approximate direction of the dipole moment for the hPEBP dimer, which suggests an orientation for the oligomer to interact with the membrane. The molecules of cacodylate present in the ligand-bound structure are shown in CPK representation. (b) Schematic topology diagram illustrating the arrangement of secondary structure in the hPEBP monomer. β Strands (shown in cyan) are labelled with lower-case letters and correspond to immunoglobulin/fibronectin type III conventions, as discussed in the text; α helices (shown in red) are labelled with upper-case letters. (The figures were prepared using the program MOLSCRIPT [32] and rendered using Raster3D [33].)

The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 1245-1254) copyright 1998.

Figure was selected by an automated process.