Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cryo-EM micrographs of HIV-1 Vif bound to human APOBEC3H, CBF-beta, ELOB, ELOC, CUL5, and RBX2

ABSTRACT:

SUBMITTER: Fumiaki Ito

PROVIDER: EMPIAR-11423 | biostudies-other |

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

Structural basis of HIV-1 Vif-mediated E3 ligase targeting of host APOBEC3H.

Ito Fumiaki F Alvarez-Cabrera Ana L AL Kim Kyumin K Zhou Z Hong ZH Chen Xiaojiang S XS

Nature communications 20230828 1

Human APOBEC3 (A3) cytidine deaminases are antiviral factors that are particularly potent against retroviruses. As a countermeasure, HIV-1 uses a viral infectivity factor (Vif) to target specific human A3s for proteasomal degradation. Vif recruits cellular transcription cofactor CBF-β and Cullin-5 (CUL5) RING E3 ubiquitin ligase to bind different A3s distinctively, but how this is accomplished remains unclear in the absence of the atomic structure of the complex. Here, we present the cryo-EM str ...[more]

PMID: 37640699

Similar Datasets

Cryo-EM micrographs of HIV-1 Vif bound to human APOBEC3H, CBF-beta, ELOB, ELOC, and N-terminal domain of CUL5

Project description: Not available

| EMPIAR-11424 | biostudies-other

Cryo-EM micrographs of APOBEC3G bound to HIV-1 Vif in comblex with CBF-beta and CUL5 E3 ligase

Project description: Not available

| EMPIAR-11339 | biostudies-other

Interactions between HIV-1 Vif and human ElonginB-ElonginC are important for CBF-? binding to Vif.

Project description:BACKGROUND: The HIV-1 accessory factor Vif is necessary for efficient viral infection in non-permissive cells. Vif antagonizes the antiviral activity of human cytidine deaminase APOBEC3 proteins that confer the non-permissive phenotype by tethering them (APOBEC3DE/3F/3G) to the Vif-CBF-?-ElonginB-ElonginC-Cullin5-Rbx (Vif-CBF-?-EloB-EloC-Cul5-Rbx) E3 complex to induce their proteasomal degradation. EloB and EloC were initially reported as positive regulatory subunits of the Elongin (SIII) complex. Thereafter, EloB and EloC were found to be components of Cul-E3 complexes, contributing to proteasomal degradation of specific substrates. CBF-? is a newly identified key regulator of Vif function, and more information is needed to further clarify its regulatory mechanism. Here, we comprehensively investigated the functions of EloB (together with EloC) in the Vif-CBF-?-Cul5 E3 ligase complex. RESULTS: The results revealed that: (1) EloB (and EloC) positively affected the recruitment of CBF-? to Vif. Both knockdown of endogenous EloB and over-expression of its mutant with a 34-residue deletion in the COOH-terminal tail (EloB?C34/EB?C34) impaired the Vif-CBF-? interaction. (2) Introduction of both the Vif SLQ ? AAA mutant (Vif?SLQ, which dramatically impairs Vif-EloB-EloC binding) and the Vif PPL ? AAA mutant (Vif?PPL, which is thought to reduce Vif-EloB binding) could reduce CBF-? binding. (3) EloB-EloC but not CBF-? could greatly enhance the folding of full-length Vif in Escherichia coli. (4) The over-expression of EloB or the N-terminal ubiquitin-like (UbL) domain of EloB could significantly improve the stability of Vif/Vif?SLQ/Vif?PPL through the region between residues 9 and 14. CONCLUSION: Our results indicate that the Vif interaction with EloB-EloC may contribute to recruitment of CBF-? to Vif, demonstrating that the EloB C-teminus may play a role in improving Vif function and that the over-expression of EloB results in Vif stabilization.

| S-EPMC3765967 | biostudies-literature

Cryo-EM micrographs of human RYBP-PRC1 bound to unmodified mononucleosome

Project description: Not available

| EMPIAR-12106 | biostudies-other

Cryo-EM micrographs of human RYBP-PRC1 bound to H2Aub1 mononucleosome

Project description: Not available

| EMPIAR-12087 | biostudies-other

Cryo-EM structure of substrate-bound human telomerase holoenzyme.

Project description:The enzyme telomerase adds telomeric repeats to chromosome ends to balance the loss of telomeres during genome replication. Telomerase regulation has been implicated in cancer, other human diseases, and ageing, but progress towards clinical manipulation of telomerase has been hampered by the lack of structural data. Here we present the cryo-electron microscopy structure of the substrate-bound human telomerase holoenzyme at subnanometre resolution, showing two flexibly RNA-tethered lobes: the catalytic core with telomerase reverse transcriptase (TERT) and conserved motifs of telomerase RNA (hTR), and an H/ACA ribonucleoprotein (RNP). In the catalytic core, RNA encircles TERT, adopting a well-ordered tertiary structure with surprisingly limited protein-RNA interactions. The H/ACA RNP lobe comprises two sets of heterotetrameric H/ACA proteins and one Cajal body protein, TCAB1, representing a pioneering structure of a large eukaryotic family of ribosome and spliceosome biogenesis factors. Our findings provide a structural framework for understanding human telomerase disease mutations and represent an important step towards telomerase-related clinical therapeutics.

| S-EPMC6223129 | biostudies-literature

CryoTransformer: A Transformer Model for Picking Protein Particles from Cryo-EM Micrographs.

Project description:Cryo-electron microscopy (cryo-EM) is a powerful technique for determining the structures of large protein complexes. Picking single protein particles from cryo-EM micrographs (images) is a crucial step in reconstructing protein structures from them. However, the widely used template-based particle picking process requires some manual particle picking and is labor-intensive and time-consuming. Though machine learning and artificial intelligence (AI) can potentially automate particle picking, the current AI methods pick particles with low precision or low recall. The erroneously picked particles can severely reduce the quality of reconstructed protein structures, especially for the micrographs with low signal-to-noise (SNR) ratios. To address these shortcomings, we devised CryoTransformer based on transformers, residual networks, and image processing techniques to accurately pick protein particles from cryo-EM micrographs. CryoTransformer was trained and tested on the largest labelled cryo-EM protein particle dataset - CryoPPP. It outperforms the current state-of-the-art machine learning methods of particle picking in terms of the resolution of 3D density maps reconstructed from the picked particles as well as F1-score and is poised to facilitate the automation of the cryo-EM protein particle picking.

| S-EPMC10634673 | biostudies-literature

Vif determines the requirement for CBF-β in APOBEC3 degradation.

Project description:APOBEC3 (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3) proteins are cellular DNA deaminases that restrict a broad spectrum of lentiviruses. This process is counteracted by Vif (viral infectivity factor) of lentiviruses, which binds APOBEC3s and promotes their degradation. CBF-β (core binding factor subunit β) is an essential co-factor for the function of human immunodeficiency virus type 1 Vif to degrade human APOBEC3s. However, the requirement for CBF-β in Vif-mediated degradation of other mammalian APOBEC3 proteins is less clear. Here, we determined the sequence of feline CBFB and performed phylogenetic analyses. These analyses revealed that mammalian CBFB is under purifying selection. Moreover, we demonstrated that CBF-β is dispensable for feline immunodeficiency virus Vif-mediated degradation of APOBEC3s of its host. These findings suggested that primate lentiviruses have adapted to use CBF-β, an evolutionary stable protein, to counteract APOBEC3 proteins of their hosts after diverging from other lentiviruses.

| S-EPMC4361795 | biostudies-literature

Cryo-EM micrographs of human ABCA1

Project description: Not available

| EMPIAR-10798 | biostudies-other

Cryo-EM micrographs of RESC1-RESC2 complex bound to gRNA

Project description: Not available

| EMPIAR-11677 | biostudies-other