Sandbox Reserved 654: Difference between revisions
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The mechanism of protein-protein interaction for the bromodomain of PCAF with histone proteins begins with the acetylation of lysine residues on the histone tail. The acetylation causes a conformational change in the histones, which allows for transcriptional machinery to access DNA. The bromodomains of PCAF within a pretranscriptional initiation complex (PIC) bind to the acetyl-lysine of the histone to stabilize the complex so that transcription may begin. The bromodomains of PCAF have three major points of contact that allow for site-specific histone recognition. First, the acetylated lysine of the target protein enters a hydrophobic pocket embedded between the ZA and BC loops at the bottom of the protein. The Asn803 residue in the bromodomain forms a hydrogen bond with the amide nitrogen of the acetyl-lysine. Next, residues in the ZA and/or BC loops interact with residues adjacent to the acetyl-lysine, which reinforces the acetyl-lysine binding in the bromodomain. Finally, additional residues in the ZA and BC loops that face opposite to the bromodomain form hydrophobic and/ or electrostatic interaction with the target protein 3 residues away from the acetyl-lysine. This residue clamps on the BC loop together with the acetyl-lysine side chain that is bound inside the hydrophobic pocket of the bromodomain.[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339198/] | The mechanism of protein-protein interaction for the bromodomain of PCAF with histone proteins begins with the acetylation of lysine residues on the histone tail. The acetylation causes a conformational change in the histones, which allows for transcriptional machinery to access DNA. The bromodomains of PCAF within a pretranscriptional initiation complex (PIC) bind to the acetyl-lysine of the histone to stabilize the complex so that transcription may begin. The bromodomains of PCAF have three major points of contact that allow for site-specific histone recognition. First, the acetylated lysine of the target protein enters a hydrophobic pocket embedded between the ZA and BC loops at the bottom of the protein. The Asn803 residue in the bromodomain forms a hydrogen bond with the amide nitrogen of the acetyl-lysine. Next, residues in the ZA and/or BC loops interact with residues adjacent to the acetyl-lysine, which reinforces the acetyl-lysine binding in the bromodomain. Finally, additional residues in the ZA and BC loops that face opposite to the bromodomain form hydrophobic and/ or electrostatic interaction with the target protein 3 residues away from the acetyl-lysine. This residue clamps on the BC loop together with the acetyl-lysine side chain that is bound inside the hydrophobic pocket of the bromodomain.[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339198/] | ||
The histone acetyltransferase portion of PCAF helps with the transactivation of HIV-1 by acetylating Lys28 of Tat. The acetylated Lys28 of Tat interacts with positive elongation factors, which stimulates elongation of nascent HIV-1 transcripts. [http://www.sciencedirect.com/science/article | The histone acetyltransferase portion of PCAF helps with the transactivation of HIV-1 by acetylating Lys28 of Tat. The acetylated Lys28 of Tat interacts with positive elongation factors, which stimulates elongation of nascent HIV-1 transcripts. [http://www.sciencedirect.com/science/article/pii/S0969212602007542] | ||
== '''Implications or Possible Applications''' == | == '''Implications or Possible Applications''' == | ||
