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Thioredoxin-dependent disulfide bond reduction is required for protamine eviction from sperm chromatin.

ABSTRACT: Cysteine oxidation in protamines leads to their oligomerization and contributes to sperm chromatin compaction. Here we identify the Drosophila thioredoxin Deadhead (DHD) as the factor responsible for the reduction of intermolecular disulfide bonds in protamines and their eviction from sperm during fertilization. Protamine chaperone TAP/p32 dissociates DNA-protamine complexes in vitro only when protamine oligomers are first converted to monomers by DHD. dhd-null embryos cannot decondense sperm chromatin and terminate development after the first pronuclear division. Therefore, the thioredoxin DHD plays a critical role in early development to facilitate the switch from protamine-based sperm chromatin structures to the somatic nucleosomal chromatin.

SUBMITTER: Emelyanov AV

PROVIDER: S-EPMC5238724 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Thioredoxin-dependent disulfide bond reduction is required for protamine eviction from sperm chromatin.

Emelyanov Alexander V AV Fyodorov Dmitry V DV

Genes & development 20161228 24

Cysteine oxidation in protamines leads to their oligomerization and contributes to sperm chromatin compaction. Here we identify the Drosophila thioredoxin Deadhead (DHD) as the factor responsible for the reduction of intermolecular disulfide bonds in protamines and their eviction from sperm during fertilization. Protamine chaperone TAP/p32 dissociates DNA-protamine complexes in vitro only when protamine oligomers are first converted to monomers by DHD. dhd-null embryos cannot decondense sperm ch ...[more]

PMID: 28031247

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Project description:Disulfide bonds influence the stability and activity of many proteins. In Escherichia coli, the DsbA and DsbB enzymes promote disulfide bond formation. Other bacteria, including the Actinobacteria, use instead of DsbB the enzyme vitamin K epoxide reductase (VKOR), whose gene is found either fused to or in the same operon as a dsbA-like gene. Mycobacterium tuberculosis and other Gram-positive actinobacteria secrete many proteins with even numbers of cysteines to the cell envelope. These organisms have predicted oxidoreductases and VKOR orthologs. These findings indicate that such bacteria likely form disulfide bonds in the cell envelope. The M. tuberculosisvkor gene complements an E. colidsbB deletion strain, restoring the oxidation of E. coli DsbA. While we have suggested that the dsbA gene linked to the vkor gene may express VKOR's partner in mycobacteria, others have suggested that two other extracytoplasmic oxidoreductases (DsbE or DsbF) may be catalysts of protein disulfide bond formation. However, there is no direct evidence for interactions of VKOR with either DsbA, DsbE, or DsbF. To identify the actual substrate of VKOR, we identified two additional predicted extracytoplasmic DsbA-like proteins using bioinformatics analysis of the M. tuberculosis genome. Using the five potential DsbAs, we attempted to reconstitute disulfide bond pathways in E. coli and in Mycobacterium smegmatis, a close relative of M. tuberculosis Our results show that only M. tuberculosis DsbA is oxidized by VKOR. Comparison of the properties of dsbA- and vkor-null mutants in M. smegmatis shows parallels to the properties of dsb mutations in E. coliIMPORTANCE Disulfide bond formation has a great impact on bacterial pathogenicity. Thus, disulfide-bond-forming proteins represent new targets for the development of antibacterials, since the inhibition of disulfide bond formation would result in the simultaneous loss of the activity of several classes of virulence factors. Here, we identified five candidate proteins encoded by the M. tuberculosis genome as possible substrates of the M. tuberculosis VKOR protein involved in disulfide bond formation. We then reconstituted the mycobacterial disulfide bond formation pathway in E. coli and showed that of the five candidates, only M. tuberculosis DsbA is efficiently oxidized by VKOR in E. coli We also present evidence for the involvement of VKOR in DsbA oxidation in M. smegmatis.

Dataset Information

Thioredoxin-dependent disulfide bond reduction is required for protamine eviction from sperm chromatin.

Publications

Thioredoxin-dependent disulfide bond reduction is required for protamine eviction from sperm chromatin.

Similar Datasets

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