Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF bromodomain.
The human immunodeficiency virus type 1 (HIV-1) trans-activator protein Tat stimulates transcription of the integrated HIV-1 genome and promotes viral replication in infected cells. Tat transactivation activity is dependent on lysine acetylation and its association with nuclear histone acetyltransferases p300/CBP (CREB binding protein) and p300/CBP-associated factor (PCAF). Here, we show that the bromodomain of PCAF binds specifically to HIV-1 Tat acetylated at lysine 50 and that this interaction competes effectively against HIV-1 TAR RNA binding to the lysine-acetylated Tat. The three-dimensional solution structure of the PCAF bromodomain in complex with a lysine 50-acetylated Tat peptide together with biochemical analyses provides the structural basis for the specificity of this molecular recognition and reveals insights into the differences in ligand selectivity of bromodomains.
Mujtaba
Shiraz
S
Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA.
He
Yan
Y
Zeng
Lei
L
Farooq
Amjad
A
Carlson
Justin E
JE
Ott
Melanie
M
Verdin
Eric
E
Zhou
Ming-Ming
MM
D000107:Acetylation; D000595:Amino Acid Sequence; D015696:Gene Products, tat / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D014764:Viral Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D008239:Lysine