WDR5 / BIG3 antibody

Background of WDR5 / BIG3 antibody

The WD40-repeat proteins are a large family of proteins found in all eukaryotes and implicated in very diverse functions such as signal transduction, vesicular trafficking, cytoskeletal assembly, cell cycle control, apoptosis and transcription regulation. A general function arttributed to WD40 contaiing proteins is to provide scaffold for protein-protein interaction and initiate/coordinate down-stream events such as ubiquitination methylation and acetylation. One of the WD40 repeat protein WDR5 directly interacts with K4 methylated H3 (1). The WDR5 interaction with K4 methylated H3 presents a novel dimethyl lysine recognition interaction which differs form chromodomain and or tudor domain interactions with acetylated histones requiring an aromatic cage to recognize methylated lysines. The interaction of WDR5 with H3K4me3 is via nonconventional hydrogen bonds involving the carboxylgroup of Glu322 (2). Other reports suggest that dimethylation of H3K4 is modestly recognize by WDR5 (3) and other report suggest that methylation state of K4 has no effect on H3 binding to WDR5 (4).
WDR5 is a highly conserved protein that shares over 90% sequence identity among all vertebrates, and 68 and 34% sequence identity with Caenorhabditis elegans and Saccharomyces cerevisiae WDR5 homologs, respectively (2). WDR5 contains seven WD40 repeats, forming a seven-blade β-propeller structure preceded by 30 amino acid unstructured loop. WDR5 is developmentally expressed in osteoblasts and is invoiced in the accelerated differentiation, suppression of WDR5 interferes with canonical Wnt signaling pathways at multiple levels and optimal levels are required for osteoblast development (5).
WDR5 is a 334 (40kDa) amino acid nuclear protein. WD40 domain, found in a number of eukaryotic proteins which contain a GH dipeptide of 11-24 amino acid in residues and is involved in a wide variety of functions such as acting like an adaptor/regulatory modules in signal transduction,pre-mRNA processing and cytoskeleton assembly. The WD40 domain of WDR5 represents a histone methyl-lysine recognition domains that is important for recruiting H3K4 methyltransferases to K4-dimethylated histone H3 tail as well as for global and gene-specific K4 trimethylation (1).