Liu Yezhou, Liu Aijun, Ye Richard D
Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China.
Dongguan Songshan Lake Central Hospital, Dongguan Third People's Hospital, The Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University, Dongguan 523326, China.
Biomedicines. 2024 Oct 28;12(11):2470. doi: 10.3390/biomedicines12112470.
Chemerin is a chemotactic adipokine that participates in a multitude of physiological processes, including adipogenesis, leukocyte chemotaxis, and neuroinflammation. Chemerin exerts biological functions through binding to one or more of its G protein-coupled receptors (GPCRs), namely chemokine-like receptor 1 (CMKLR1), G protein-coupled receptor 1 (GPR1), and CC-motif receptor-like 2 (CCRL2). Of these receptors, CMKLR1 and GPR1 have been confirmed as signaling receptors of chemerin, whereas CCRL2 serves as a chemerin-binding protein without transmembrane signaling. High-resolution structures of two chemerin receptors are now available thanks to recent advancements in structure biology. This review focuses on the structural perspectives of the chemerin receptors with an emphasis on the structure-activity correlation, including key components of the two receptors for ligand recognition and conformational changes induced by chemerin and its derivative peptides for G protein activation. There are also comparisons between the two chemerin receptors and selected GPCRs with peptide ligands for better appreciation of the shared and distinct features of the chemerin receptors in ligand recognition and transmembrane signaling, and in the evolution of this subclass of GPCRs.
Chemerin是一种趋化性脂肪因子，参与多种生理过程，包括脂肪生成、白细胞趋化性和神经炎症。Chemerin通过与其一种或多种G蛋白偶联受体（GPCR）结合发挥生物学功能，这些受体即趋化因子样受体1（CMKLR1）、G蛋白偶联受体1（GPR1）和CC基序受体样2（CCRL2）。在这些受体中，CMKLR1和GPR1已被确认为Chemerin的信号受体，而CCRL2作为一种Chemerin结合蛋白，不具有跨膜信号传导功能。由于结构生物学的最新进展，现在已有两种Chemerin受体的高分辨率结构。本综述重点关注Chemerin受体的结构观点，强调结构-活性相关性，包括两种受体用于配体识别的关键组分以及Chemerin及其衍生肽诱导的用于G蛋白激活的构象变化。还对两种Chemerin受体与选定的具有肽配体的GPCR进行了比较，以便更好地理解Chemerin受体在配体识别和跨膜信号传导以及该GPCR亚类进化中的共同和独特特征。
