User:Brian Boyle/Sandbox 1

spinqualitylabelsall models Apo BRPF1 Bromodomain solved via solution NMR. (PDB entry 2d9e) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Overview Peregrin, also known as Bromodomain and PHD Finger-containing 1 (BRPF1) is a 137 kDa protein that plays a versatile role in epigenetic signaling events. It contains three chromatin reader domains, including a bromodomain, PZP domain (two PDH fingers separated by a Zinc Knuckle), and proline-tryptophan-tryptophan-proline (PWWP) domain . Through these three domains, it is capable of recognizing both modified and unmodified histones, as well as non-specifically binding DNA ,. BRPF1 carries out its function as a component of the MOZ (monocytic leukemic zinc-finger protein) histone acetyltransferase (HAT) complex . This complex is involved in the regulation of gene expression, particularly those involved with skeletal development and hematopoiesis ,. Acetyllysine Binding The BRPF1 bromodomain has been shown to recognize and bind to various acetylated lysine marks on the N-terminal tails of histones tails . Using isothermal titration calorimetry (ITC) experiments, it was found that the BRPF1 bromodomain preferentially binds to histone H4 acetylated at positions K5 (2rs9) and K12 (4qyd) as well as H2A at position K5 (4qyl) ,. Interestingly, the BRPF1 bromodomain has also been shown to bind di-acetylated histone peptides with high affinity, including H4K5acK8ac and H4K5acK12ac . Acetyllysine recognition is coordinated by a number of residues in the bromodomain's binding pocket. Using NMR chemical shift perturbation experiments, Glass et al. reported several key residues involved in coordinating histone H4 ligands (I27, L34, E36, V37, N83, and I88). Notably, asparagine 83 was among these. The interactions between the amide nitrogen of asparagine with the carbonyl of the acetyllysine group is conserved among bromodomains and is necessary for binding to occur ,. Role in Disease Progression BRPF1 has been implicated in the progression of several cancers. Chromosomal translocations of the gene encoding BRPF1 have been linked to the development of acute myeloid leukemia . Another study reported an association between upregulation of the BRPF1 gene and poor survival rates in hepatocellular carcinoma patients . Mutations within the gene itself have been associated with neurological disorders and widespread reduced histone acetylation .

Proteopedia Page Contributors and Editors (what is this?)

Brian Boyle