title: Structural basis for ELL2 and AFF4 activation of HIV-1 proviral transcription.
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.
authors.affiliation: Department of Urology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and National Collaborative Innovation Center, Chengdu 610041, China.|Department of Molecular and Cell Biology and California Institute of Quantitative Biosciences, University of California, Berkeley, Berkeley, California 94720, USA.
authors.forename: Shiqian
authors.initials: S
authors.lastname: Qi
authors.affiliation: Department of Molecular and Cell Biology and California Institute of Quantitative Biosciences, University of California, Berkeley, Berkeley, California 94720, USA.
authors.forename: Zichong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Molecular and Cell Biology and California Institute of Quantitative Biosciences, University of California, Berkeley, Berkeley, California 94720, USA.
authors.forename: Ursula
authors.initials: U
authors.lastname: Schulze-Gahmen
authors.affiliation: Department of Molecular and Cell Biology and California Institute of Quantitative Biosciences, University of California, Berkeley, Berkeley, California 94720, USA.|Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
authors.forename: Goran
authors.identifier: 0000-0002-4841-9949
authors.initials: G
authors.lastname: Stjepanovic
authors.affiliation: Department of Molecular and Cell Biology and California Institute of Quantitative Biosciences, University of California, Berkeley, Berkeley, California 94720, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Molecular and Cell Biology and California Institute of Quantitative Biosciences, University of California, Berkeley, Berkeley, California 94720, USA.|Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Hurley
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000821:virology; D001665:Binding Sites / Q000235:genetics; D064113:CRISPR-Cas Systems; D018360:Crystallography, X-Ray; D015967:Gene Expression Regulation, Viral; D055786:Gene Knockout Techniques; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D016296:Mutagenesis; D011485:Protein Binding / Q000235:genetics; D000072417:Protein Domains / Q000235:genetics; D011533:Proviruses / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D061805:Transcription Elongation, Genetic / Q000502:physiology*; D035602:Transcriptional Elongation Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014775:Virus Activation / Q000235:genetics; D017735:Virus Latency / Q000235:genetics; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: C471348:AFF4 protein, human; C447613:ELL2 protein, human; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D035602:Transcriptional Elongation Factors; D054322:tat Gene Products, Human Immunodeficiency Virus