# H-dependent modulation of tetrahydromethanopterin S-methyltransferase (Mtr complex) activity by the small protein MtrR in Methanosarcina mazei.
> メタノサルシナ・マゼイにおける小タンパク質MtrRによるテトラヒドロメタノプテリンS-メチルトランスフェラーゼ（Mtr複合体）活性のH2依存的調節


## Abstract

This study characterizes MtrR, a 49-amino-acid small protein encoded by ORF16 in the mesophilic archaeon Methanosarcina mazei. MtrR was found to form oligomers at the cytoplasmic membrane, where it physically associates with the membrane-bound tetrahydrosarcinapterin S-methyltransferase (Mtr) complex, a central component of archaeal energy metabolism. In vitro interaction assays, in vivo copurification experiments, and microscale thermophoresis collectively confirmed a specific binding interaction with the MtrA subunit of the complex. Growth experiments under varying H2 concentrations revealed that deletion of mtrR significantly impaired growth in the presence of H2, regardless of carbon source. Additionally, mtrR transcription was induced under H2-replete conditions. These findings support a model in which MtrR acts as a fine-tuning regulator of Mtr complex activity in response to fluctuating environmental H2 levels, enabling metabolic adaptation in this archaeal organism.

### Mechanism

Under H2-rich conditions, mtrR transcription is upregulated, and the resulting MtrR protein binds specifically to the MtrA subunit of the Mtr complex, modulating its S-methyltransferase activity and enabling metabolic adaptation to changing H2 availability in archaea.

## Bibliographic

- **Authors**: Habenicht T, Hastedt B, Cassidy L, Kießling C, Tholey A, Schuller JM, et al.
- **Journal**: FEBS J
- **Year**: 2026 (2026-02-13)
- **PMID**: [41689349](https://pubmed.ncbi.nlm.nih.gov/41689349/)
- **DOI**: [10.1111/febs.70457](https://doi.org/10.1111/febs.70457)
- **Study type**: in vitro study
- **Delivery route**: in vitro
- **Effect reported**: positive

## Delivery context

This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).

## Safety notes

This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 41689349. https://h2-papers.org/en/papers/41689349
> **Source**: PubMed PMID [41689349](https://pubmed.ncbi.nlm.nih.gov/41689349/)