9U78

Single Chain Protein of De Novo Designed Helix Bundles-4EH2 with KDPV Loop

Summary for 9U78

• Entry DOI: 10.2210/pdb9u78/pdb
• Descriptor: Single Chain Protein of De Novo Designed Helix Bundles-4EH2 with KDPV Loop, ZINC ION, ACETATE ION, ... (6 entities in total)
• Functional Keywords: de novo protein, helix bundles, single chain, metalloprotein
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 29190.04

Authors

Du, G.M.,Zhang, S.-Q.,Liu, L.J. (deposition date: 2025-03-24, release date: 2025-04-09, Last modification date: 2025-06-18)

Primary citation

Hatstat, A.K.,Kormos, R.,Xu, V.,Du, G.,Liu, L.,Zhang, S.Q.,DeGrado, W.F.
A Designed Zn 2+ Sensor Domain Transmits Binding Information to Transmembrane Histidine Kinases.
J.Am.Chem.Soc., 147:18770-18782, 2025

PubMed Abstract: Generating stimulus-responsive allosteric signaling is a significant challenge in protein design. In natural systems like bacterial histidine kinases (HKs), signal transduction occurs when ligand binding initiates a signal that is amplified across biological membranes over long distances to induce large-scale rearrangements and phosphorylation relays. Here, we ask whether our understanding of protein design and multidomain, intramolecular signaling has progressed sufficiently to enable engineering of a HK with tunable components. We generated metal-binding sensor domains and substituted them for the native sensor domain of a transmembrane HK, affording chimeras that transduce signals initiated from a sensor. Signaling depended on the designed sensor's stability and the interdomain linker's phase and length. These results show the usefulness of design to elucidate the biochemical mechanisms and principles of transmembrane signaling.

PubMed: 40388352
DOI: 10.1021/jacs.5c02273

Experimental method

X-RAY DIFFRACTION (1.7 Å)