生物化学系M. Madan Babu课题组在研究中取得进展。他们报道了人类趋化因子GPCR相互作用网络的编码和解码选择性和滥交。这一研究成果于2025年4月23日发表在国际顶尖学术期刊《细胞》上。
该研究团队确定了由趋化因子及其受体编码和解码的保守的、半保守的和可变的决定因素（即识别元件），以介导相互作用。选择性和混杂性来自于分布在结构化和非结构化蛋白质区域的广义（“公共/保守”）和特异性（“私有/可变”）决定因素的集合，配体和受体组合地识别这些决定因素。该课题组人员利用这些原理设计了一种具有改变GPCR偶联偏好的病毒趋化因子，并提供了一种网络抗性，以促进序列-结构-功能研究和蛋白质设计工作，以开发免疫疗法和细胞疗法。
据介绍，在人类中，46种分泌的趋化因子配体和g蛋白偶联受体（GPCR）家族的23种细胞表面趋化因子受体之间的选择性和混杂相互作用形成了一个复杂的网络来协调细胞迁移。虽然趋化因子和它们的GPCR都有共同的结构支架，但驱动选择性和滥交的分子原理仍然是未知的。
附：英文原文
Title: Encoding and decoding selectivity and promiscuity in the human chemokine-GPCR interaction network
Author: Andrew B. Kleist, Martyna Szpakowska, Lindsay J. Talbot, Greg Slodkowicz, Duccio Malinverni, Monica A. Thomas, Kyler S. Crawford, Daniel J. McGrail, Acacia F. Dishman, Michael J. Wedemeyer, Madison Sluter, S. Stephen Yi, Nidhi Sahni, Francis C. Peterson, Andy Chevigné, Brian F. Volkman, M. Madan Babu
Issue&Volume: 2025-04-23
Abstract: In humans, selective and promiscuous interactions between 46 secreted chemokine ligands and 23 cell surface chemokine receptors of the G-protein-coupled receptor (GPCR) family form a complex network to coordinate cell migration. While chemokines and their GPCRs each share common structural scaffolds, the molecular principles driving selectivity and promiscuity remain elusive. Here, we identify conserved, semi-conserved, and variable determinants (i.e., recognition elements) that are encoded and decoded by chemokines and their receptors to mediate interactions. Selectivity and promiscuity emerge from an ensemble of generalized (“public/conserved”) and specific (“private/variable”) determinants distributed among structured and unstructured protein regions, with ligands and receptors recognizing these determinants combinatorially. We employ these principles to engineer a viral chemokine with altered GPCR coupling preferences and provide a web resource to facilitate sequence-structure-function studies and protein design efforts for developing immuno-therapeutics and cell therapies.
DOI: 10.1016/j.cell.2025.03.046
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00398-8