9ZZO

MP1104-bound Kappa Opioid Receptor in complex with beta-arrestin1

Summary for 9ZZO

• Entry DOI: 10.2210/pdb9zzo/pdb
• EMDB information: 75011
• Descriptor: Nanobody 32, Isoform 1B of Beta-arrestin-1, Kappa-type opioid receptor,Vasopressin V2 receptor, ... (7 entities in total)
• Functional Keywords: gpcr, kappa opioid receptor, signaling protein-immune system complex, signaling protein/immune system
• Biological source: Lama glama (llama); More
• Total number of polymer chains: 5
• Total formula weight: 146237.06

Authors

Han, J.,Chen, M.,Che, T. (deposition date: 2026-01-07, release date: 2026-06-17)

Primary citation

Han, J.,Fine, E.J.,Jiang, Q.,Zhuang, Y.,Suomivuori, C.M.,Chen, Z.W.,Denn, E.,Whiddon, K.,Li, K.,Evers, A.S.,Fuller, J.,Carter, J.,Fay, J.F.,Chen, M.,Dror, R.O.,Che, T.
Structural dynamics of kappa opioid receptor interactions with beta-arrestin 1.
Nat Commun, 2026

PubMed Abstract: Opioid receptors signal through Gi/o protein and β-arrestin pathways that mediate distinct effects of opiate drugs. While opioid binding and G protein activation are well studied, β-arrestin recruitment remains poorly understood. Here, we determine the complex structure of the kappa opioid receptor (KOR) with β-arrestin1 (βarr1) at 2.60 Å resolution using cryogenic electron microscopy. Structural and mass spectrometry analyses reveal multiple phosphorylation sites and a phospholipid-binding site that specifically enhances arrestin recruitment. The KOR-βarr1 complex adopts a core interaction and exhibits notable differences from other GPCR-βarr1 complexes. Comparisons with the structures of KOR-Nb39 and KOR-Gi1 complexes also reveal distinct structural features in the orthosteric binding site and the KOR-transducer interface that affect signaling bias. Using extensive 3D variation analysis and molecular dynamics simulations, we identify a range of conformational dynamics in both the receptor and βarr1, suggesting an allosteric pathway for arrestin's entry and exit.

PubMed: 42243110
DOI: 10.1038/s41467-026-73968-3

Experimental method

ELECTRON MICROSCOPY (2.6 Å)