Characterization of neuromedin U (NMU), neuromedin S (NMS) and their receptors (NMUR1, NMUR2) in chickens

Wan, Ying; Zhang, Jiannan; Fang, Chao; Chen, Junan; Li, Jing; Li, Juan; Wu, Chao; Wang, Yajun

doi:10.1016/j.peptides.2017.12.022

Cited by 17 publications

(16 citation statements)

References 66 publications

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“…Extensive efforts have been devoted to understanding the peptide-binding mechanisms of NMUR subtypes. Both NMU and NMS share the highly conserved C-terminal heptapeptide (FLFRPRN-NH 2 ) and the amidated asparagine at the C-terminus across different species 9 , 14 , 15 , indicative of the importance of this conserved peptide segment for receptor recognition. Indeed, this heptapeptide is strongly related to the binding activity, with even single amino acid substitutions reducing their biological effects 16 – 18 .…”

Section: Introductionmentioning

confidence: 99%

Structural insights into the peptide selectivity and activation of human neuromedin U receptors

You

Zhang

et al. 2022

Nat Commun

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Neuromedin U receptors (NMURs), including NMUR1 and NMUR2, are a group of Gq/11-coupled G protein-coupled receptors (GPCRs). NMUR1 and NMUR2 play distinct, pleiotropic physiological functions in peripheral tissues and in the central nervous system (CNS), respectively, according to their distinct tissue distributions. These receptors are stimulated by two endogenous neuropeptides, neuromedin U and S (NMU and NMS) with similar binding affinities. NMURs have gathered attention as potential drug targets for obesity and inflammatory disorders. Specifically, selective agonists for NMUR2 in peripheral tissue show promising long-term anti-obesity effects with fewer CNS-related side effects. However, the mechanisms of peptide binding specificity and receptor activation remain elusive. Here, we report four cryo-electron microscopy structures of Gq chimera-coupled NMUR1 and NMUR2 in complexes with NMU and NMS. These structures reveal the conserved overall peptide-binding mode and the mechanism of peptide selectivity for specific NMURs, as well as the common activation mechanism of the NMUR subfamily. Together, these findings provide insights into the molecular basis of the peptide recognition and offer an opportunity for the design of the selective drugs targeting NMURs.

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Section: Introductionmentioning

confidence: 99%

Structural insights into the peptide selectivity and activation of human neuromedin U receptors

You

Zhang

et al. 2022

Nat Commun

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“…We included 18 studies [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] with 1422 participants, 736 in the treatment group and 686 in the control group, all of which were published in Chinese between 2003 and 2021. Since there were many forms of acupuncture, such as electric acupuncture, fre acupuncture, screw acupuncture, moxibustion, and so on.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Te experimental intervention group included acupuncture, and the experimental control group included Chinese medicine and Western medicine. Te included studies were divided into three groups based on the intervention in the experiment and the control groups: ① acupuncture versus Western medicine (n � 9) [24][25][26][27][28][29][30][31][32]; ② acupuncture plus Western medicine versus Western medicine (n � 4) [33][34][35][36]; ③ acupuncture plus Chinese medicine versus Chinese medicine (n � 5) [37][38][39][40][41]. Study characteristics of the included literature were summarized and listed in Table 2.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…All included randomized controlled trials had low risk in domain 3 and domain 5. In terms of the overall risk of bias of the included studies, 2 studies [24,26] were high risk and 16 [25,[27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] studies were some concerns. Te risk of the bias table is shown in Figures 2 and 3.…”

Section: Risk Of Bias In Includedmentioning

confidence: 99%

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A Systematic Review and Meta-Analysis of Acupuncture Treatment for Oral Ulcer

Yan

Chen

Zuo

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Oral ulcer (OU) is a common oral mucosal disease manifested with obvious pain. In some studies, the efficacy of acupuncture in OU has been confirmed, but systematic reviews and meta-analyses for them are lacking. Our aim is to evaluate the efficacy of acupuncture in the treatment of OU. Methods. We searched the literature from eight databases from their inception to December 2021. We included randomized controlled trials of acupuncture for the treatment of oral ulcer. The meta-analysis was carried out using Review Manager 5.3 and Stata 16.0. The main outcomes were the effective rate and the recurrence rate, the secondary outcomes were the visual analogue score (VAS) and the ulcer healing time. Results. Totally, 18 studies were finally included in the meta-analysis, including 1,422 patients. In meta-analyses, we found that in comparison with Western medicine, acupuncture can improve effective rate (OR = 5.40, 95% CI: 3.40 to 8.58), reduce the ulcer recurrence rate (OR = 0.21, 95% CI: 0.13 to 0.33), and relieve the ulcer pain (MD = −2.26, 95% CI: −4.27to−0.24). In addition, compared with Western medicine, acupuncture plus Western medicine also can improve effective rate (OR = 2.95, 95% CI: 1.48 to 5.85). Compared with the Chinese medicine, the acupuncture plus Chinese medicine can improve the effective rate (OR = 8.26, 95% CI: 3.61 to 18.88) and relieve the ulcer pain (MD = −1.85, 95% CI: −2.51 to −1.19). Conclusion. Acupuncture may be more effective than Western medicine in terms of efficacy rate, and acupuncture combined with Western or Chinese medicine may have the potential to reduce the recurrence of ulcer and relieve the ulcer pain. However, due to limited evidence, higher quality and more rigorously designed clinical trials with larger sample sizes will be needed to further confirm our findings.

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“…Extensive efforts have been devoted to understanding the peptide-binding mechanisms of NMUR subtypes. Both NMU and NMS share the highly conserved C-terminal heptapeptide (FLFRPRN-NH2) and the amidated asparagine at the C-terminus across different species 9,14,15 , indicative of the importance of this conserved peptide segment for receptor recognition. Indeed, this heptapeptide is strongly related to the binding activity, with even single amino acid substitutions reducing their biological effects [16][17][18] .…”

Section: Introductionmentioning

confidence: 99%

Structural insights into the peptide selectivity and activation of human neuromedin U receptors

You

Zhang

et al. 2022

Preprint

View full text Add to dashboard Cite

Neuromedin U receptors (NMURs), including NMUR1 and NMUR2, are a group of Gq/11-coupled G protein-coupled receptors (GPCRs) related to pleiotropic physiological functions. Upon stimulation by two endogenous neuropeptides, neuromedin U and S (NMU and NMS) with similar binding affinities, NMUR1 and NMUR2 primarily display distinct peripheral tissue and central nervous system (CNS) functions, respectively, due to their distinct tissue distributions. These NMU receptors have triggered extensive attention as drug targets for obesity and immune inflammation. Specifically, selective agonists for NMUR1 in peripheral tissue show promising long-term anti-obesity effects with fewer CNS-related side effects. However, the mechanisms of peptide binding specificity and receptor activation remain elusive due to the lack of NMU receptor structures, which hamper drug design targeting NMU receptors. Here, we report four cryo-electron microscopy structures of Gq chimera-coupled NMUR1 and NMUR2 bound with NMU and NMS. These structures present the conserved overall peptide-binding mode and reveal the mechanism of peptide selectivity for specific NMURs, as well as the common activation mechanism of the NMUR subfamily. Together, these findings provide insights into the molecular basis of the peptide recognition selectivity and offer a new opportunity for designing selective drugs targeting NMURs.

show abstract

Characterization of neuromedin U (NMU), neuromedin S (NMS) and their receptors (NMUR1, NMUR2) in chickens

Cited by 17 publications

References 66 publications

Structural insights into the peptide selectivity and activation of human neuromedin U receptors

Structural insights into the peptide selectivity and activation of human neuromedin U receptors

A Systematic Review and Meta-Analysis of Acupuncture Treatment for Oral Ulcer

Structural insights into the peptide selectivity and activation of human neuromedin U receptors

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