title: Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF bromodomain.
abstract: 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.
authors.affiliation: Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA.
authors.forename: Shiraz
authors.initials: S
authors.lastname: Mujtaba
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.forename: Lei
authors.initials: L
authors.lastname: Zeng
authors.forename: Amjad
authors.initials: A
authors.lastname: Farooq
authors.forename: Justin E
authors.initials: JE
authors.lastname: Carlson
authors.forename: Melanie
authors.initials: M
authors.lastname: Ott
authors.forename: Eric
authors.initials: E
authors.lastname: Verdin
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Zhou
mesh_terms: 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
chemical_list: D015696:Gene Products, tat; D014764:Viral Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D008239:Lysine