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[[Image:1bd9.gif|left|200px]]<br /><applet load="1bd9" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1bd9, resolution 2.05&Aring;" />
'''HUMAN PHOSPHATIDYLETHANOLAMINE BINDING PROTEIN'''<br />


==Overview==
==HUMAN PHOSPHATIDYLETHANOLAMINE BINDING PROTEIN==
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.
<StructureSection load='1bd9' size='340' side='right'caption='[[1bd9]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
 
== Structural highlights ==
==Disease==
<table><tr><td colspan='2'>[[1bd9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BD9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BD9 FirstGlance]. <br>
Known diseases associated with this structure: Cleidocranial dysplasia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600211 600211]], Dental anomalies, isolated OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600211 600211]]
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05&#8491;</td></tr>
 
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1bd9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bd9 OCA], [https://pdbe.org/1bd9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bd9 RCSB], [https://www.ebi.ac.uk/pdbsum/1bd9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bd9 ProSAT]</span></td></tr>
==About this Structure==
</table>
1BD9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BD9 OCA].
== Function ==
 
[https://www.uniprot.org/uniprot/PEBP1_HUMAN PEBP1_HUMAN] Binds ATP, opioids and phosphatidylethanolamine. Has lower affinity for phosphatidylinositol and phosphatidylcholine. Serine protease inhibitor which inhibits thrombin, neuropsin and chymotrypsin but not trypsin, tissue type plasminogen activator and elastase (By similarity). Inhibits the kinase activity of RAF1 by inhibiting its activation and by dissociating the RAF1/MEK complex and acting as a competitive inhibitor of MEK phosphorylation.<ref>PMID:18294816</ref>  HCNP may be involved in the function of the presynaptic cholinergic neurons of the central nervous system. HCNP increases the production of choline acetyltransferase but not acetylcholinesterase. Seems to be mediated by a specific receptor (By similarity).<ref>PMID:18294816</ref>
==Reference==
== Evolutionary Conservation ==
Function from structure? The crystal structure of human phosphatidylethanolamine-binding protein suggests a role in membrane signal transduction., Banfield MJ, Barker JJ, Perry AC, Brady RL, Structure. 1998 Oct 15;6(10):1245-54. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9782050 9782050]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bd/1bd9_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1bd9 ConSurf].
<div style="clear:both"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Banfield, M J.]]
[[Category: Banfield MJ]]
[[Category: Barker, J J.]]
[[Category: Barker JJ]]
[[Category: Brady, R L.]]
[[Category: Brady RL]]
[[Category: Perry, A C.F.]]
[[Category: Perry ACF]]
[[Category: lipid-binding]]
[[Category: signalling]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:54:09 2008''

Latest revision as of 09:35, 7 February 2024

HUMAN PHOSPHATIDYLETHANOLAMINE BINDING PROTEINHUMAN PHOSPHATIDYLETHANOLAMINE BINDING PROTEIN

Structural highlights

1bd9 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.05Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PEBP1_HUMAN Binds ATP, opioids and phosphatidylethanolamine. Has lower affinity for phosphatidylinositol and phosphatidylcholine. Serine protease inhibitor which inhibits thrombin, neuropsin and chymotrypsin but not trypsin, tissue type plasminogen activator and elastase (By similarity). Inhibits the kinase activity of RAF1 by inhibiting its activation and by dissociating the RAF1/MEK complex and acting as a competitive inhibitor of MEK phosphorylation.[1] HCNP may be involved in the function of the presynaptic cholinergic neurons of the central nervous system. HCNP increases the production of choline acetyltransferase but not acetylcholinesterase. Seems to be mediated by a specific receptor (By similarity).[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

  1. ↑ Rath O, Park S, Tang HH, Banfield MJ, Brady RL, Lee YC, Dignam JD, Sedivy JM, Kolch W, Yeung KC. The RKIP (Raf-1 Kinase Inhibitor Protein) conserved pocket binds to the phosphorylated N-region of Raf-1 and inhibits the Raf-1-mediated activated phosphorylation of MEK. Cell Signal. 2008 May;20(5):935-41. doi: 10.1016/j.cellsig.2008.01.012. Epub 2008, Jan 24. PMID:18294816 doi:http://dx.doi.org/10.1016/j.cellsig.2008.01.012
  2. ↑ Rath O, Park S, Tang HH, Banfield MJ, Brady RL, Lee YC, Dignam JD, Sedivy JM, Kolch W, Yeung KC. The RKIP (Raf-1 Kinase Inhibitor Protein) conserved pocket binds to the phosphorylated N-region of Raf-1 and inhibits the Raf-1-mediated activated phosphorylation of MEK. Cell Signal. 2008 May;20(5):935-41. doi: 10.1016/j.cellsig.2008.01.012. Epub 2008, Jan 24. PMID:18294816 doi:http://dx.doi.org/10.1016/j.cellsig.2008.01.012

1bd9, resolution 2.05Å

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