27EM

Cryo_EM structure of PACAP27_PAC1R_Beta_arrestin 1 complex

Summary for 27EM

• Entry DOI: 10.2210/pdb27em/pdb
• EMDB information: 81097
• Descriptor: Beta-arrestin-1, Fab30H, Fab30L, ... (6 entities in total)
• Functional Keywords: gpcr, beta arrestin1, membrane protein/immune system, membrane protein-immune system complex
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 146506.52

Authors

Zhao, L.,Yuan, Q.,Zhang, M. (deposition date: 2026-05-28, release date: 2026-09-16)

Primary citation

Zhang, M.,Li, X.,Yuan, Q.N.,Hu, W.,Xu, H.E.,Zhao, L.H.
Structural basis of beta-arrestin coupling and transducer selectivity in PAC1R.
Acta Pharmacol.Sin., 2026

PubMed Abstract: The pituitary adenylate cyclase-activating polypeptide receptor (PAC1R) is a class B G protein-coupled receptor (GPCR) that engages both G proteins and β-arrestins to mediate diverse signaling responses, yet how PAC1R adopts distinct intracellular conformations to achieve this transducer selectivity remains poorly understood. Here, we report the cryo-electron microscopy structure of PAC1R in complex with β-arrestin 1 (βarr1), revealing a core-engaged conformation. Comparison with the G-bound PAC1R structure shows that βarr1 engagement is associated with remodeling of the intracellular transmembrane bundle, including TM5 reorientation and inward movement of TM6, resulting in a receptor core geometry distinct from that of the G protein-bound state. Comparison with the βarr1-bound parathyroid hormone receptor 1 (PTH1R) structure further reveals both conserved and receptor-specific features of βarr1 engagement. Although outward displacement of the TM5 cytoplasmic end is observed in both PAC1R-βarr1 and PTH1R-βarr1 complexes, its specific direction and the resulting TM5-TM6 rearrangements differ between receptors, correlating with distinct βarr1 finger loop orientations within the receptor core. Together, these findings suggest that β-arrestin core engagement by class B GPCRs is accompanied by receptor-specific intracellular remodeling that may contribute to transducer selectivity in PAC1R.

PubMed: 42706324
DOI: 10.1038/s41401-026-01924-4

Experimental method

ELECTRON MICROSCOPY (3 Å)