1xhn

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|PDB= 1xhn |SIZE=350|CAPTION= <scene name='initialview01'>1xhn</scene>, resolution 1.95&Aring;
|PDB= 1xhn |SIZE=350|CAPTION= <scene name='initialview01'>1xhn</scene>, resolution 1.95&Aring;
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|LIGAND= <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>
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|ACTIVITY=
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xhn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xhn OCA], [http://www.ebi.ac.uk/pdbsum/1xhn PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1xhn RCSB]</span>
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[[Category: beta-barrel]]
[[Category: beta-barrel]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:09:56 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:49:45 2008''

Revision as of 21:49, 30 March 2008


PDB ID 1xhn

Drag the structure with the mouse to rotate
, resolution 1.95Å
Ligands:
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



The crystal structure of Cellular Repressor of E1A-stimulated Genes (CREG)


Overview

The cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein that inhibits proliferation and enhances differentiation of human embryonal carcinoma cells. CREG binds to the cation-independent mannose 6-phosphate (M6P)/insulin-like growth factor II (IGF2) receptor (IGF2R) (M6P/IGF2R), and this receptor has been shown to be required for CREG-induced growth suppression. To better understand CREG function in cellular growth and differentiation, we solved the 3D crystal structure of this protein to 1.9-A resolution. CREG forms a tight homodimeric complex, and CREG monomers display a beta-barrel fold. The three potential glycosylation sites on CREG map to a confined patch opposite the dimer interface. Thus, dimerization of glycosylated CREG likely presents a bivalent ligand for the M6P/IGF2R. Closely related structural homologs of CREG are FMN-binding split-barrel fold proteins that bind flavin mononucleotide. Our structure shows that the putative flavin mononucleotide-binding pocket in CREG is sterically blocked by a loop and several key bulky residues. A mutant of CREG lacking a part of this loop maintained overall structure and dimerization, as well as M6P/IGF2R binding, but lost the growth suppression activity of WT CREG. Thus, analysis of a structure-based mutant of CREG revealed that binding to M6P/IGF2R, while necessary, is not sufficient for CREG-induced growth suppression. These findings indicate that CREG utilizes a known fold for a previously undescribed function [corrected]

About this Structure

1XHN is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The crystal structure of CREG, a secreted glycoprotein involved in cellular growth and differentiation., Sacher M, Di Bacco A, Lunin VV, Ye Z, Wagner J, Gill G, Cygler M, Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18326-31. Epub 2005 Dec 12. PMID:16344469

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