Structural basis for ELL2 and AFF4 activation of HIV-1 proviral transcription
Open Access
- 30 January 2017
- journal article
- research article
- Published by Springer Nature in Nature Communications
- Vol. 8 (1) , 14076
Abstract
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.Keywords
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This publication has 30 references indexed in Scilit:
- Latency reversal and viral clearance to cure HIV-1Science, 2016
- Eradicating HIV-1 infection: seeking to clear a persistent pathogenNature Reviews Microbiology, 2014
- Transcriptional control of HIV latency: Cellular signaling pathways, epigenetics, happenstance and the hope for a cureVirology, 2014
- AFF1 is a ubiquitous P-TEFb partner to enable Tat extraction of P-TEFb from 7SK snRNP and formation of SECs for HIV transactivationProceedings of the National Academy of Sciences, 2013
- An Integrated Overview of HIV-1 LatencyCell, 2013
- The Super Elongation Complex Family of RNA Polymerase II Elongation Factors: Gene Target Specificity and Transcriptional OutputMolecular and Cellular Biology, 2012
- Function of leukemogenic mixed lineage leukemia 1 (MLL) fusion proteins through distinct partner protein complexesProceedings of the National Academy of Sciences, 2011
- HIV-1 Tat and Host AFF4 Recruit Two Transcription Elongation Factors into a Bifunctional Complex for Coordinated Activation of HIV-1 TranscriptionMolecular Cell, 2010
- HIV-1 Tat Assembles a Multifunctional Transcription Elongation Complex and Stably Associates with the 7SK snRNPMolecular Cell, 2010
- P-TEFb, a Cyclin-Dependent Kinase Controlling Elongation by RNA Polymerase IIMolecular and Cellular Biology, 2000