Stent protein BRPF2 regulates the molecular basis of myST family acetyl transferase HBO1 for histogene H3K14 acetylase activity.

On February 24th Nucleic Acid Research, an international academic journal, published online the latest findings of the Ding Jianping Research Group of the National Protein Science Center of the Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences (Shanghai): Structural and mechanistic insights into regulation of HBO 1 histone acetyltransferase activityy by BRPF2, the study revealed the molecular basis of stent protein BRPF2 regulating myST family acetyl transferase HBO1 for histone H3K14 acetylase activity.
acetylation of alloproteins is an important preceptogenetic modification, which is closely related to the assembly form of chromatin, especially the degree of chromatin disaturation and loosening.
different degrees of acetylation determine the expression of chromatin-specific bit genes, and further affect DNA replication and repair, cell differentiation and development of a variety of physiological processes.
in the body, histone acetyltransferase (HAT) is responsible for acetylation of lysine residues at specific points on histogens.
HBO1 belongs to the MYST histone acetyl transferase family and has broad-spectrum enzyme activity for H3, H4 and other non-histone substrates.
in vivo it is able to form stable complexes with stent proteins BRPF or JADE and auxiliary proteins ING4/5 and Safe6.
different component compositions determine HBO1's location on chromatin, while enhancing its acetylase activity at specific points.
study showed that the HBO1-BRPF2 complex was able to specifically acetylase histoprotein H3K14 in the body, and that abnormal levels of acetylation at that point could lead to DNA replication, cell cycle disorders, embryo developmental retardation and tumor occurrence.
refore, studying the assembly of the HBO1-BRPF2 complex and the way the compound regulates the activity of the HBO1 enzyme can improve the understanding of the molecular mechanisms of how the hismoprotein acetyl transferase complex performs its physiological function.
Ding Jianping Research Group phD student Tao Ye and associate researcher Zhong Wei and others found that the N-side fragments of BRPF2 can form a stable complex with the HBO1 catalytic domain, the formation of which in-body can promote HBO1 for histone H3K14 acetylase activity.
then, using structural biology methods to analyze the crystal structure of the compound in combination with cofactor acetyl coenzyme A, the researchers found that HBO1 presented a classic MYST domain configuration, while BRPF2 specifically combined with a b-card structure at the C end of HBO1.
They further used biochemistry and cell biology to verify and analyze the interaction between HBO1 and BRPF2, identified the key points involved in specific identification, and found that the interaction between HBO1 and BRPF2 was significantly different from the previously reported interaction between MYST family protein MOP and stent protein MSL1.
addition, in vivo experimental results also prove that the N-side region of BRPF2 is an important site for HBO1-BRPF2 interaction, and that the region can assist the compound to some extent to bind to the nucleosome.
results not only reveal the molecular basis for BRPF2 to regulate HBO1 enzyme activity, but also provide important information for further elo-esoteric regulation mechanisms of other histogenic acetyl transferase complexes.
the 19U line station of the National Protein Science Research Facility (Shanghai) provided support and assistance in the collection of crystal diffraction data.
research has been supported by the National Natural Science Foundation of China, the Chinese Academy of Sciences and the Ministry of Science and Technology.
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