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| - | [[Image:1xhn.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1xhn.png|left|200px]] |
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| | {{STRUCTURE_1xhn| PDB=1xhn | SCENE= }} | | {{STRUCTURE_1xhn| PDB=1xhn | SCENE= }} |
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| - | '''The crystal structure of Cellular Repressor of E1A-stimulated Genes (CREG)'''
| + | ===The crystal structure of Cellular Repressor of E1A-stimulated Genes (CREG)=== |
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| - | ==Overview==
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| - | 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] | + | The line below this paragraph, {{ABSTRACT_PUBMED_16344469}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 16344469 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_16344469}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Sacher, M.]] | | [[Category: Sacher, M.]] |
| | [[Category: Beta-barrel]] | | [[Category: Beta-barrel]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 15:02:43 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 03:23:26 2008'' |
Revision as of 00:23, 28 July 2008
Template:STRUCTURE 1xhn
The crystal structure of Cellular Repressor of E1A-stimulated Genes (CREG)
Template:ABSTRACT PUBMED 16344469
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
Page seeded by OCA on Mon Jul 28 03:23:26 2008
