6K7P

Crystal structure of human AFF4-THD domain

6K7P の概要

• エントリーDOI: 10.2210/pdb6k7p/pdb
• 分子名称: AF4/FMR2 family member 4 (2 entities in total)
• 機能のキーワード: super elongation complex, aff4, hiv-1, dimerizaiton, transcription
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30469.62

構造登録者

Tang, D.,Xue, Y.,Li, S.,Cheng, W.,Duan, J.,Wang, J.,Qi, S. (登録日: 2019-06-08, 公開日: 2020-03-11, 最終更新日: 2024-03-27)

主引用文献

Tang, D.,Chen, C.,Liao, G.,Liu, J.,Liao, B.,Huang, Q.,Chen, Q.,Zhao, J.,Jiang, H.,Duan, J.,Huang, J.,Wang, K.,Wang, J.,Zhou, C.,Chu, W.,Li, W.,Sun, B.,Li, Z.,Dai, L.,Fu, X.,Cheng, W.,Xue, Y.,Qi, S.
Structural and functional insight into the effect of AFF4 dimerization on activation of HIV-1 proviral transcription.
Cell Discov, 6:7-7, 2020

PubMed Abstract: Super elongation complex (SEC) is a positive regulator of RNA polymerase II, which is required for HIV-1 proviral transcription. AFF1/4 is the scaffold protein that recruits other components of SEC and forms dimer depending on its THD domain (TPRL with Handle Region Dimerization Domain). Here we report the crystal structure of the human AFF4-THD at the resolution of 2.4 Å. The α4, α5, and α6 of one AFF4-THD mediate the formation of a dimer and pack tightly against the equivalent part of the second molecule in the dimer of AFF-THD. Mutagenesis analysis revealed that single mutations of either Phe1014 or Tyr1096 of AFF4 to alanine impair the formation of the AFF4 dimer. In addition, transactivation assay also indicated that Phe1014 and Tyr1096 of AFF4 are critical to the transactivation activity of AFF4. Interestingly, the corresponding residues Phe1063 and Tyr1145 in AFF1 have an effect on the transactivation of HIV-1 provirus. However, such mutations of AFF1/4 have no effect on the interaction of AFF1/4 with other subunits of the SEC. Together, our data demonstrated that the dimerization of AFF1/4 is essential to transactivation of HIV-1 provirus.

PubMed: 32128251
DOI: 10.1038/s41421-020-0142-6

実験手法

X-RAY DIFFRACTION (2.4 Å)