Abstract
High mobility group proteins (HMGs) are the most abundant non-histone nuclear proteins that bind to DNA and nucleosomes, modulate their conformation, increase their binding affinity with transcriptional factors and control gene expression.1 Among those HMGs, HMGA1a is a prototype member in HMGA family, which is recognized as a hub of nuclear functions to affect a plethora of normal biological processes. It consists of 106 amino acids with three “AT hooks” as DNA binding domains and an acidic tail at the C-terminus. Basically, post-translational modifications on HMGA1a proteins such as lysine acetylation, lysine/arginine methylation and serine/threonine phosphorylation play essential roles in modulating their nuclear activities.2 However, function of some PTMs are still not be well known. Recently, our group used Fmoc-protected SPPS strategy and Ser/Thr Ligation3 method, successfully developed a chemical strategy to synthesize HMGA1a protein as well as HMGA1a analogs with different post-translational modifications on the certain sites.4 By testing NMR of those HMGA1a analogs, we investigate the structure change effected by a certain PTM. At the same time, some functional groups such as Biotin and photo-reactive cross-linker are coupled onto those HMGA1a proteins, which will help to investigate their bio-activities. Together with proteomics, the binding partner of different PTMs will also be studied.
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