Cell Res: Significant progress! Wang Mingwei/Xu Huaqiang/Zhang Yan teamed up to reveal the unique hormone recognition function of GLP-2R

GLUP-like peptides (GLP-1 and GLP-2) are two types of intestinal hormones derived from glutatrogygen that mediat different physiological functions through two related subjects (GLP-1R and GLP-2R), which are important drug targets for metabolic disorders and Crohn's disease.
although significant progress has been made in the determination of GLP-1R structures, understanding of the differences in peptide binding and signal transductivity between these two subjects remains elusive.
November 25, 2020, Wang Mingwei, Xu Huaqiang and Zhang Yan of Zhejiang University of the Chinese Academy of Sciences published a research paper entitled "A unique hormonal documentation of the people glucagon-like peptide-2 receptor" online in Cell Research, a study on the frozen electron microscope structure of the complex of GLP-2R and GLP-2 and Gs heterogeneums.
in order to adapt to GLP-2 instead of GLP-1, GLP-2R fine-tunes the composition of the extracellular parts of the trans-membrane helix (TMs) and the outer ring of the cell (ECL1).
contrary to GLP-1, GLP-2's N-end histamine penetrates into the nucleation of the subject in a unique direction.
the intermediate region of GLP-2 is more widely combined with TM1 and TM7 than with ECL2, and the GLP-2 C end is closely connected to ECL1, which is most prominent in Class 9 B G protein coupled binds (GPCR).
the above three parts of GLP-2 are essential for GLP-2 identification and subject activation, especially in the middle region.
results provide new insights into the molecular basis of matching specificity in Class B GPCR and may promote the development of more specific therapies.
GLP-2R belongs to the Class B GPCR sub-family and is mainly expressed in the intestines, pancreas and brain.
its endogeneic complex is GLP-2, a member of the glutatro glutatrogen-like peptide family, which also includes GLP-1 and glutatrogygen.
GLP-2 is encoded by the pre-gluatic glucosin gene and becomes active after translation of the pre-hormone conversion enzyme.
as gastrointestinal hormone, it mainly regulates the growth and function of intestinal cortectal cells, which is essential for nutrient absorption.
like GLP-1, GLP-2 is rapidly inactivate in the body by a dispeptide peptide enzyme.
clinically, the GLP-2 similar, teduglutide, is used to treat short bowel syndrome and Crohn's disease.
is currently developing other treatments for allergies, including colitis, gastrointestinal disease in children and inflammation of the intestinal mucous membranes.
study of animal models shows that GLP-2 is critical to glucose stability, spontaneous hypertension and depression, prompting renewed attention to the role of the peptide outside the gastrointestinal tract.
cryo-EM is the primary method for determining the structure of GPCR-G protein complexes, starting with GLP-1R and calcitonin-reducing complexes, followed by eight other class B GPCR and various G protein complexes.
these structures show that Class B GPCR has a common activation mode, which is basically consistent with the previously proposed two-structure domain binding model.
class B subjects have roughly the same activation pattern, molecular details are subject-specific, especially in the mating area.
, it is important to explore the recognition mechanism between GLP-2 and GLP-2R to further understand the mechanism of match recognition and subject activation between Class B GPCR.
study, cryo-EM was used to determine the high-resolution structure of GLP-2R in people who were complex with Gs proteins.
Based on previous experience, nanoBiT strategies have been used to stabilize GLP-2-GLP-2R-Gs complexes and enhance the interaction between GLP-2R and G beta, thus forming a frozen EM structure with a resolution of 3.0?
the study data provides a reasonable template for the design of better GLP-2 similars for treatment and expands understanding of the family biology of the subject.
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