Ribbe Hu Labs

Congratulations to Bryan Neumann from our collaborator Shane Gonen’s lab on receiving the Barbara K. Burgess Postdoctoral Fellowship Award — a well-deserved honor!
@gonenshane.bsky.social‬ @ribbehulab.bsky.social @ucibiosci.bsky.social

Thanks for your kind words Joe!

Thanks for your kind words Sven!

Thanks for your kind words!

Heterologous synthesis of a simplified nitrogenase analog in Escherichia coli Heterologous synthesis of a nitrogenase analog (NifH/NifEN) in E. coli enables N2 reduction and incorporation of N into biomass.

Our second paper that came online within a week 😊! Thanks everyone for their hard work!
@ribbehulab.bsky.social @ucibiosci.bsky.social
Heterologous synthesis of a simplified nitrogenase analog in Escherichia coli | Science Advances www.science.org/doi/10.1126/...

Cryo-EM captures the coordination of asymmetric electron transfer through a di-copper site in DPOR Nature Communications - CryoEM snapshots of the nitrogenase-like DPOR protein complex captured during turnover reveal that asymmetric conformational changes, substrate recognition, and an interplay...

Our story detailing how asymmetry in nitrogenase-like proteins regulate electron transfer reactions is finally out! rdcu.be/ejaeK Congratulations to postdoc @rajnandani.bsky.social and fantastic collaborators. Thanks to funding from the Department of Energy and the NIH.

Belt-sulfur mobilization as a crucial mechanistic feature shared between the vanadium and molybdenum nitrogenases Nitrogenase catalyzes the reduction of N2 to NH3 at its active site cofactor. Catalysis by the homologous V- and Mo-nitrogenases involves the same dynamic belt-S mobilization that occurs asymmetricall...

Excited to share our latest work highlighting the crucial role of belt-sulfur mobilization in nitrogenase catalysis. A big thank you to everyone who contributed to this effort!
@cp-chemcatalysis.bsky.social @ucibiosci.bsky.social
www.cell.com/chem-catalys...

Frataxin Traps Low Abundance Quaternary Structure to Stimulate Human Fe–S Cluster Biosynthesis Iron–sulfur clusters are essential protein cofactors synthesized in human mitochondria by an NFS1-ISD11-ACP-ISCU2-FXN assembly complex. Surprisingly, researchers have discovered three distinct quaternary structures for cysteine desulfurase subcomplexes, which display similar interactions between NFS1-ISD11-ACP protomeric units but dramatically different dimeric interfaces between the protomers. Although the role of these different architectures is unclear, possible functions include regulating activity and promoting the biosynthesis of distinct sulfur-containing biomolecules. Here, crystallography, native ion-mobility mass spectrometry, and chromatography methods reveal the Fe–S assembly subcomplex exists as an equilibrium mixture of these different quaternary structures. Isotope labeling and native mass spectrometry experiments show that the NFS1-ISD11-ACP complexes disassemble into protomers, which can then undergo exchange reactions and dimerize to reform native complexes. Single crystals isolated in distinct architectures have the same activity profile and activation by the Friedreich’s ataxia (FRDA) protein frataxin (FXN) when rinsed and dissolved in assay buffer. These results suggest FXN functions as a “molecular lock” and shifts the equilibrium toward one of the architectures to stimulate the cysteine desulfurase activity and promote iron–sulfur cluster biosynthesis. An NFS1-designed variant similarly shifts the equilibrium and partially replaces FXN in activating the complex. We propose that eukaryotic cysteine desulfurases are unusual members of the morpheein class of enzymes that control their activity through their oligomeric state. Overall, the findings support architectural switching as a regulatory mechanism linked to FXN activation of the human Fe–S cluster biosynthetic complex and provide new opportunities for therapeutic interventions of the fatal neurodegenerative disease FRDA.

pubs.acs.org/doi/10.1021/...

Structural basis of inhibition of human NaV1.8 by the tarantula venom peptide Protoxin-I - Nature Communications Animal toxins can modulate action potentials and are important leads for therapeutics. Here, the authors use cryo-EM to show the interaction of the tarantula venom peptide Protoxin-I with a human volt...

Our #CryoEM study on the binding of a Tarantula toxin to a full-length human voltage-gated sodium channel has been published. Very proud of the awesome people in my lab 🥳🥂

www.nature.com/articles/s41...