Comparative domain modeling of human EGF-like module EMR2 and study of interaction of the fourth domain of EGF with chondroitin 4-sulphate

Abstract

EMR2 is an EGF-like module containing mucin-like hormone receptor-2 precursor, a G-protein coupled receptor (G-PCR). Mutation in EMR2 causes complicated disorders like polycystic kidney disease (PKD). The structure of EMR2 shows that the fifth domain is comprised of EGF-TM7 helices. Functional assignment of EMR2 by support vector machine (SVM) revealed that along with transporter activity, several novel functions are predicted. A twenty amino acid sequence “MGGRVFLVFLAFCVWLTLPG” acts as the signal peptide responsible for posttranslational transport. Eight amino acids are involved in N-glycosylation sites and two cleavage sites are Leu517 and Ser518 in EMR2. The residue Arg241 is responsible for interaction with glycosaminoglycan and chondroitin sulfate. On the basis of structure, function and ligand binding sites, competitive EMR2 inhibitors designed may decrease the rate of human diseases like Usher's syndrome, bilateral frontoparietal polymicrogyria and PKD.

Computational Analysis of the 3-D structure of Human GPR87 Protein: Implications for Structure-Based Drug Design

“…Interaction study with some other protein i.e. EMR2 in H sapiens with chondroitin 4-sulphate is reported (Rani et al, 2011), TLR4 in H sapiens (Das et al, 2012) and GAPDH protein in Leishmania were already been reported (Sahoo et al, 2013). GPCR-membrane models would provide a significant tools for studying receptor behavior and its modulation by small drug-like ligands, a relevant issue for drug discovery (Sadiq et al, 2013).…”

Affinity Binding of EMR2 Expressing Cells by Surface-Grafted Chondroitin Sulfate B

“…The (EGF)-like module-containing mucin-like hormone receptor-like 2 precursor (EMR2, also known as CD312) is a cell surface protein receptor of the EGF-TM7 family expressed by cells of the immune system, a prompt for a wide range of biological events, including adhesion and migration of cells. − The fourth EGF domain of EMR2 has been shown to interact with CS-B. , Interaction between those two entities is believed to play a role in the interaction between B cells and activated T cells, macrophages or dendritic cells, thus, potentiating the effects of pro-inflammatory response. , EMR2 expression was recently identified on a population of nonadherent endothelial progenitor cells (naEPCs; see data deposited in the NCBI gene expression omnibus (GEO Accession number: GSE25979)). , These circulating EPCs are of major interest as they are capable of in vivo vascularization, while showing low immunogenicity and rapid expansion in response to interleukin-3. , The potential of these cells for clinical application raises the question of how they can be harnessed, via novel strategies, for transplantation. , …”