Home Men's Health Boosting protein stability and resilience with interlocking rings

Boosting protein stability and resilience with interlocking rings

Boosting protein stability and resilience with interlocking rings


This examine is led by Prof. Wen-Bin Zhang (Faculty of Chemistry and Molecular Engineering, Peking College & Beijing Academy of Synthetic Intelligence) and Dr. Jing Fang (Faculty of Chemistry and Molecular Engineering, Peking College). A single-domain protein catenane refers to 2 mechanically interlocked polypeptide rings that fold synergistically right into a compact and built-in construction, which is extraordinarily uncommon in nature. This design was achieved by rewiring the connectivity between secondary motifs to introduce synthetic entanglement, and synthesis was readily achieved via a sequence of programmed streamlined post-translational processing occasions in cells with none extra in vitro reactions.

The one-domain catenane cat-DHFR was completely characterised. Proof from mixed SDS-PAGE, SEC, LC-MS, IMS-MS, and proteolytic digestion experiments unambiguously proved its topology. The cat-DHFR reveals enhanced anti-aggregation properties and has a Tm that’s 6 °C increased than the linear management. Though the catalytic exercise of cat-DHFR is decreased owing to its decreased affinity towards the substrate and cofactor, it has higher thermal resilience than l-DHFR. Even after incubation at 70 °C for 10 min, cat-DHFR retained over 70% of the catalytic exercise, whereas the linear management misplaced virtually all exercise. The analysis group anticipate that this technique might be typically relevant to different single-domain proteins, together with these with folds just like DHFR or with fully totally different folds. The supply of those single-domain protein catenanes facilitates the elucidation of topological results on construction–property relationships. The outcomes additional suggest that it’s potential to map the present linear protein universe into single-domain protein catenanes with well-preserved capabilities and extra advantages, opening up new territory for protein molecules. Surpassing the linear paradigm of pure protein molecules, these topological proteins are multi-chain, multi-dimensional molecules with practical advantages of topology, wealthy design risk and wonderful evolvability. As a brand new class of protein molecules, they maintain nice potential for a broad vary of functions, together with, however not restricted to, industrial enzymes, antibodies, cytokines, and biomaterials.


Journal reference:

Fang, J., et al. (2023). A Single-domain Protein Catenane of Dihydrofolate Reductase. Nationwide Science Evaluation. doi.org/10.1093/nsr/nwad304.



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