1xhn
From Proteopedia
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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
Page seeded by OCA on Mon Nov 12 20:05:52 2007
