Dataset Information

Structure of the yeast Bre1 RING domain.

ABSTRACT: Monoubiquitination of histone H2B at Lys123 in yeast plays a critical role in regulating transcription, mRNA export, DNA replication, and the DNA damage response. The RING E3 ligase, Bre1, catalyzes monoubiquitination of H2B in concert with the E2 ubiquitin-conjugating enzyme, Rad6. The crystal structure of a C-terminal fragment of Bre1 shows that the catalytic RING domain is preceded by an N-terminal helix that mediates coiled-coil interactions with a crystallographically related monomer. Homology modeling suggests that the human homologue of Bre1, RNF20/RNF40, heterodimerizes through similar coiled-coil interactions.

SUBMITTER: Kumar P

PROVIDER: S-EPMC4452286 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Structure of the yeast Bre1 RING domain.

Kumar Pankaj P Kumar Pankaj P Wolberger Cynthia C

Proteins 20150429 6

Monoubiquitination of histone H2B at Lys123 in yeast plays a critical role in regulating transcription, mRNA export, DNA replication, and the DNA damage response. The RING E3 ligase, Bre1, catalyzes monoubiquitination of H2B in concert with the E2 ubiquitin-conjugating enzyme, Rad6. The crystal structure of a C-terminal fragment of Bre1 shows that the catalytic RING domain is preceded by an N-terminal helix that mediates coiled-coil interactions with a crystallographically related monomer. Homol ...[more]

PMID: 25864391

Similar Datasets

Project description:Switching between different morphotypes is an adaptive cellular response in many microbes. In Cryptococcus neoformans, the yeast-to-hypha transition confers resistance to microbial predation in the soil and is an integral part of its life cycle. Morphogenesis is also known to be associated with virulence, with the filamentous form being immune-stimulatory and protective in mammalian models of cryptococcosis. Previous studies identified the transcription factor Znf2 as a master regulator of cryptococcal filamentation. However, the upstream regulators of Znf2 remain largely unknown. PAS domain proteins have long been recognized as transducers of diverse environmental signals. Here, we identified a PAS domain protein Pas3 as an upstream regulator of Znf2. Surprisingly, this small Pas3 protein lacks a nuclear localization signal but is enriched in the nucleus where it regulates the transcript level of ZNF2 and its prominent downstream targets. We discovered that the PAS domain is essential for Pas3's nuclear enrichment and function. Intriguingly, Pas3 interacts with Bre1, which is required for Cryptococcus histone H2B monoubiquitination (H2Bub1) and H3 lysine 4 dimethylation (H3K4me2), two histone modifications known to be associated with active gene transcription. Indeed, Bre1 functions together with Pas3 in regulating cryptococcal filamentation based on loss-of-function, epistasis, and transcriptome analysis. These findings provide the first evidence of a signaling regulator acting with a chromatin modifier to control cryptococcal filamentation.IMPORTANCE For the ubiquitous environmental pathogen Cryptococcus neoformans, the morphological transition from yeast to filament confers resistance to natural predators like soil amoeba and is an integral differentiation event to produce infectious spores. Interestingly, filamentation is immuno-stimulatory and attenuates cryptococcal virulence in a mammalian host. Consistently, the morphogenesis transcription factor Znf2 profoundly shapes cryptococcal interaction with various hosts. Identifying the signaling pathways activating filamentation is thus, conductive to a better understanding of cryptococcal biology. In this study, we identified a PAS domain protein Pas3 that functions upstream of Znf2 in regulating cryptococcal filamentation. Interestingly, Pas3 interacts with the chromatin modifier Bre1 in the nucleus to regulate the transcript level of Znf2 and its prominent downstream targets. This is the first example of a PAS domain signaling regulator interacting with a chromatin modifier to control filamentation through their impact on cryptococcal transcriptome.

Dataset Information

Structure of the yeast Bre1 RING domain.

Publications

Structure of the yeast Bre1 RING domain.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets