Structure of the super-elongation complex subunit AFF4 C-terminal homology domain reveals requirements for AFF homo- and heterodimerization.
Amino Acid Sequence
Crystallography, X-Ray
DNA
/ chemistry
Dimerization
Humans
Phosphorylation
Positive Transcriptional Elongation Factor B
/ metabolism
Protein Folding
Protein Structure, Tertiary
Protein Subunits
/ chemistry
RNA
/ chemistry
Recombinant Proteins
/ biosynthesis
Sequence Alignment
Substrate Specificity
Transcriptional Elongation Factors
/ chemistry
AF4/FMR2 family member 4 (AFF4)
C-terminal homology domain (CHD)
RNA polymerase II
X-ray crystallography
dimerization
gene regulation
phosphorylation
super elongation complex
transcription elongation factor
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
05 07 2019
05 07 2019
Historique:
received:
01
04
2019
revised:
27
05
2019
pubmed:
31
5
2019
medline:
11
3
2020
entrez:
1
6
2019
Statut:
ppublish
Résumé
AF4/FMR2 family member 4 (AFF4) is the scaffold protein of the multisubunit super-elongation complex, which plays key roles in the release of RNA polymerase II from promoter-proximal pausing and in the transactivation of HIV-1 transcription. AFF4 consists of an intrinsically disordered N-terminal region that interacts with other super-elongation complex subunits and a C-terminal homology domain (CHD) that is conserved among AF4/FMR2 family proteins, including AFF1, AFF2, AFF3, and AFF4. Here, we solved the X-ray crystal structure of the CHD in human AFF4 (AFF4-CHD) to 2.2 Å resolution and characterized its biochemical properties. The structure disclosed that AFF4-CHD folds into a novel domain that consists of eight helices and is distantly related to tetratrico peptide repeat motifs. Our analyses further revealed that AFF4-CHD mediates the formation of an AFF4 homodimer or an AFF1-AFF4 heterodimer. Results from fluorescence anisotropy experiments suggested that AFF4-CHD interacts with both RNA and DNA
Identifiants
pubmed: 31147444
pii: S0021-9258(20)31855-X
doi: 10.1074/jbc.RA119.008577
pmc: PMC6615702
doi:
Substances chimiques
AFF4 protein, human
0
Protein Subunits
0
Recombinant Proteins
0
Transcriptional Elongation Factors
0
RNA
63231-63-0
DNA
9007-49-2
Positive Transcriptional Elongation Factor B
EC 2.7.11.-
Banques de données
PDB
['6GKG-F']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10663-10673Informations de copyright
© 2019 Chen and Cramer.
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