Date of Award

2011

Degree Type

Thesis

Degree Name

Master of Science

Program

Biochemistry

Supervisor

Dr. Hong Ling

Abstract

Cysteine-Rich Protein 2 Binding Partner (CRP2BP) is a novel human protein, which is involved in chromatin metabolism. CRP2BP, referred to as Atac in this study, is implicated in histone modification. The N-terminus of Atac (AtacN) contains a predicted plant homeo domain (PHD) in its N-terminal fragment. We characterized AtacN through structural and functional studies by using biochemical and biophysical methods, such as circular dichroism and interaction assays. Sequence analysis of AtacN indicated that it had substantially unordered components. An unusual thermally-induced aggregation had been observed in stability assays. Interestingly, AtacN indiscriminately bound non- and tri-methylated histone tails. Further binding studies on different truncations indicated that the L50-G64 region is important for trimethylated histone 4 lysine 20 (H4K20me3) binding. Strong binding to phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) and weak binding to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) was also detected. AtacN’s ability to bind both phospholipid and histone ligands implies that Atac may link lipid-signalling and gene expression.

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