Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10870581 | FEBS Letters | 2014 | 11 Pages |
Abstract
Bromodomain-PHD finger protein 1 (BRPF1) is part of the MOZ HAT complex and contains a unique combination of domains typically found in chromatin-associated factors, which include plant homeodomain (PHD) fingers, a bromodomain and a proline-tryptophan-tryptophan-proline (PWWP) domain. Bromodomains are conserved structural motifs generally known to recognize acetylated histones, and the BRPF1 bromodomain preferentially selects for H2AK5ac, H4K12ac and H3K14ac. We solved the X-ray crystal structures of the BRPF1 bromodomain in complex with the H2AK5ac and H4K12ac histone peptides. Site-directed mutagenesis on residues in the BRPF1 bromodomain-binding pocket was carried out to investigate the contribution of specific amino acids on ligand binding. Our results provide critical insights into the molecular mechanism of ligand binding by the BRPF1 bromodomain, and reveal that ordered water molecules are an essential component driving ligand recognition.
Keywords
CBPTIF2AMLBRPF1ING5NCOA3ZNFHOXMOZHSCsPHDhomeoboxHDACPTMITCnuclear magnetic resonanceSite-directed mutagenesispost-translational modificationZinc fingerEpigeneticsX-ray crystallographyNMRcircular dichroismhematopoietic stem cellsacute myeloid leukemiaHistone acetyltransferasehistone deacetylaseCREB binding proteinMolecular dynamicIsothermal titration calorimetryHATplant homeodomain
Related Topics
Life Sciences
Agricultural and Biological Sciences
Plant Science
Authors
Mulu Y. Lubula, Brian E. Eckenroth, Samuel Carlson, Amanda Poplawski, Maksymilian Chruszcz, Karen C. Glass,