HIV-1 Tat recruits transcription elongation factors dispersed along a flexible AFF4 scaffold

Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):E123-31. doi: 10.1073/pnas.1216971110. Epub 2012 Dec 18.


The HIV-1 Tat protein stimulates viral gene expression by recruiting human transcription elongation complexes containing P-TEFb, AFF4, ELL2, and ENL or AF9 to the viral promoter, but the molecular organization of these complexes remains unknown. To establish the overall architecture of the HIV-1 Tat elongation complex, we mapped the binding sites that mediate complex assembly in vitro and in vivo. The AFF4 protein emerges as the central scaffold that recruits other factors through direct interactions with short hydrophobic regions along its structurally disordered axis. Direct binding partners CycT1, ELL2, and ENL or AF9 act as bridging components that link this complex to two major elongation factors, P-TEFb and the PAF complex. The unique scaffolding properties of AFF4 allow dynamic and flexible assembly of multiple elongation factors and connect the components not only to each other but also to a larger network of transcriptional regulators.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites / genetics
  • Blotting, Western
  • Circular Dichroism
  • Cyclin T / metabolism
  • Electrophoresis
  • Escherichia coli
  • Gene Expression Regulation, Viral / physiology*
  • HIV-1*
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Luciferases
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Positive Transcriptional Elongation Factor B / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcriptional Elongation Factors / genetics
  • Transcriptional Elongation Factors / metabolism*
  • tat Gene Products, Human Immunodeficiency Virus / metabolism*


  • AFF4 protein, human
  • CCNT1 protein, human
  • Cyclin T
  • ELL protein, human
  • ELL2 protein, human
  • Multiprotein Complexes
  • Repressor Proteins
  • Transcriptional Elongation Factors
  • tat Gene Products, Human Immunodeficiency Virus
  • Luciferases
  • Positive Transcriptional Elongation Factor B