Structural basis for ELL2 and AFF4 activation of HIV-1 proviral transcription

Qi, Shiqian; Li, Zichong; Schulze-Gahmen, Ursula; Stjepanovic, Goran; Zhou, Qiang; Hurley, James H.

doi:10.1038/ncomms14076

Structural basis for ELL2 and AFF4 activation of HIV-1 proviral transcription

Journal Article · Mon Jan 30 00:00:00 EST 2017 · Nature Communications

DOI:https://doi.org/10.1038/ncomms14076· OSTI ID:1623870

Qi, Shiqian ^[1]; Li, Zichong ^[2]; Schulze-Gahmen, Ursula ^[2]; ^[3]; Zhou, Qiang ^[2]; Hurley, James H. ^[3]

Sichuan Univ., Chengdu (China); Univ. of California, Berkeley, CA (United States); DOE/OSTI
Univ. of California, Berkeley, CA (United States)
Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

The intrinsically disordered scaffold proteins AFF1/4 and the transcription elongation factors ELL1/2 are core components of the super elongation complex required for HIV-1 proviral transcription. Here we report the 2.0-Å resolution crystal structure of the human ELL2 C-terminal domain bound to its 50-residue binding site on AFF4, the ELLBow. The ELL2 domain has the same arch-shaped fold as the tight junction protein occludin. The ELLBow consists of an N-terminal helix followed by an extended hairpin that we refer to as the elbow joint, and occupies most of the concave surface of ELL2. This surface is important for the ability of ELL2 to promote HIV-1 Tat-mediated proviral transcription. The AFF4–ELL2 interface is imperfectly packed, leaving a cavity suggestive of a potential binding site for transcription-promoting small molecules.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); SLAC National Accelerator Lab., Menlo Park, CA (United States)

Sponsoring Organization:: National Institutes of Health (NIH); National Natural Science Foundation of China (NSFC); USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-05CH11231; AC02-76SF00515

OSTI ID:: 1623870

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 8; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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