Arrestins comprise a family of signal regulators of G-protein-coupled receptors (GPCRs), which include arrestins 1 to 4. While arrestins 1 and 4 are visual arrestins dedicated to rhodopsin, arrestins 2 and 3 (Arr2 and Arr3) are β-arrestins known to regulate many nonvisual GPCRs. The dynamic and promiscuous coupling of Arr2 to nonvisual GPCRs has posed technical challenges to tackle the basis of arrestin binding to GPCRs. Here we report the structure of Arr2 in complex with neurotensin receptor 1 (NTSR1), which reveals an overall assembly that is strikingly different from the visual arrestin-rhodopsin complex by a 90°rotation of Arr2 relative to the receptor. In this new configuration, intracellular loop 3 (ICL3) and transmembrane helix 6 (TM6) of the receptor are oriented toward the N-terminal domain of the arrestin, making it possible for GPCRs that lack the C-terminal tail to couple Arr2 through their ICL3. Molecular dynamics simulation and crosslinking data further support the assembly of the Arr2-NTSR1 complex. Sequence analysis and homology modeling suggest that the Arr2-NTSR1 complex structure may provide an alternative template for modeling arrestin-GPCR interactions.

This work is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license. Contents 1 Background and objectives 3 Operations 7 Lithostratigraphy 21 Biostratigraphy 24 Paleomagnetism 27 Structural geology 33 Geochemistry 37 Physical properties 40 Downhole measurements 42 Logging while drilling 49 Core-log-seismic integration 56 Observatory 61 References

Aim Intrauterine growth retardation (IUGR) is a prevalent problem in mammals. The present study was conducted to unveil the alterations in intestinal microbiota in IUGR piglets. Methods and Results We identified the alterations of small intestinal microbiota in IUGR piglets on 7, 21 and 28 days of age using 16S rRNA sequencing. The results showed that IUGR piglets had a decreased alpha diversity of jejunum microbiota at 7 and 21 days of age; had lower abundances of Bacteroidetes and Bacteroides in the jejunum at 7, 21 and 28 days of age, Oscillibacter in the jejunum at 21 days of age, and Firmicutes in the ileum at 21 days of age; whereas they had higher abundances of Proteobacteria and Pasteurella in the ileum at 21 days of age and Escherichia–Shigella in the jejunum at 28 days of age. Correlation analysis showed that Bacteroides, Oscillibacter and Ruminococcaceae_UCG‐002 compositions were positively associated with the body weight (BW) of IUGR piglets, nevertheless Proteobacteria and Escherichia–Shigella relative abundances were negatively correlated with the BW of IUGR piglets. Gene function prediction analysis indicated that microbiota‐associated carbohydrate metabolism, lipid metabolism, glycan biosynthesis and metabolism, amino acid metabolism, and xenobiotics biodegradation and metabolism were downregulated in the IUGR piglets compared to control piglets. Conclusions The present study profiled the intestinal microbiota of newborn piglets with IUGR and the newborn IUGR piglets have lower diversity and different taxonomic abundances. Alterations in the abundances of Bacteroidetes, Bacteroides, Proteobacteria Escherichia–Shigella and Pasteurella may be involved in nutrient digestion and absorption, as well as the potential mechanisms connecting to the growth and development of IUGR in mammals. Significance and Impact of the Study The small intestinal microbiota were highly shaped in the IUGR piglets, which might further mediate the growth and development of IUGR piglets; and the gut microbiota could serve as a potential target for IUGR treatment.