Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2022 Nov 16;13:7013. doi: 10.1038/s41467-022-34629-3

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

PMC Copyright notice

Fig. 6 — a–c Cryo-EM maps of the receptor-alone focused refinements of VPAC1R-VIP (green), VPAC1R-PACAP27 (blue) and PAC1R-PACAP27 (pink) shown as side view with a zoom onto the ECD Helix 1 and ECL1. Maps are shown in transparent and model backbones are shown in ribbon format. The relevant cysteines are shown as stick models, with the putative disulfide bond present. Due to ambiguity, the disulfide bond was not modelled in the final, deposited models, however, the relevant cysteine residues are in a position to potentially form a bond. Cysteines of interest are labelled according to their residue number: Cys37 (ECD) and Cys208 (ECL1) of the VPAC1R and Cys25 (ECD) and Cys219 (ECL1) of the PAC1R. d–e Differences in cAMP potency (pEC50) derived from concentration response analysis (data in Supplementary Fig. 13 comparing wild-type receptors to alanine mutant receptors lacking the relevant cysteines); d pEC50 of WT and C37A and C208A VPAC1R single mutations in response to PACAP38 (orange), PACAP27 (black) and VIP (dark cyan); e: pEC50 of WT, C25A, C219A and C25A/C219A in response to PACAP38 (blue), PACAP27 (red) and VIP (green). The data for panels d and e are the mean ± SEM, n = 3 independent experiments. Differences in potency between WT and mutant receptors was assessed using a one-way ANOVA and Dunnett’s post-test. Statistically Significant changes (p < 0.05) are indicated with asterisk (*). f Tabular comparison of N-terminal peptide residues (H1, S2, D3) hydrogen bonds with receptor residues, comparing the presence and absence of the ECD-ECL1 disulfide bond during the MD equilibrium simulation from the experimental structures of VPAC1R-PACAP27, PAC1R-PACAP27 and VPAC1R-VIP, and the PAC1R-VIP homology model. Interactions are listed by percentage of occupancy of frames, with the background colouring representing maximum occupancy % (red) and minimum occupancy % (white). Receptor residue background colouring is according to their residue numbering (TM transmembrane helix, ECL3 extracellular loop 3). Table is based on data presented in Supplementary Table 4. Source data for panels d and e are provided in the Source Data file.