@article {46807,
	title = {G-protein coupled receptors and tau-different roles in alzheimer{\textquoteright}s disease},
	journal = {Neuroscience},
	volume = {438},
	year = {2020},
	month = {JUL },
	pages = {198-214},
	type = {Article},
	abstract = {<p>Post-translational modification of Tau, a microtubule-associated protein in the neuronal cell, plays a major role in Alzheimer{\textquoteright}s disease. Tau is an axonal protein expressed in mature neurons that promote the self-assembly of tubulin into microtubules and its stabilization in neurons. Phosphorylation of Tau makes it prone to aggregation at the intra-neuronal region leading to impaired neurotransmission and dementia. Tau aggregates undergo trans-cellular propagation by the release of fibrillar species into the extra-cellular environment from damaged and infected neurons that can be internalized by neighbouring neuronal and glia cells and promotes aggregation in healthy cells. G-protein coupled receptors, the largest group of seven transmembrane receptors, are involved in neuronal signal transduction in response to various signals such as hormones and neurotransmitters. In Alzheimer{\textquoteright}s disease, GPCRs are involved in phosphorylation of Tau through various downstream kinases such as GSK-3b, CDK-5 and ERKs signalling cascade. Several neuronal GPCRs that are involved in Tau phosphorylation are elaborated in this review. The astrocytic GPCR, Tau phosphorylation mediated by CaS receptors and its propagation by exosomes are also elaborated. In the microglia, the extra-cellular Tau binding to a chemokine GPCR, CX3CR1 triggers its internalization, whereas Tau phosphorylation at specific sites decreases its binding affinity to this receptor. Here we highlight the role of GPCRs in Tau phosphorylation and Tau interaction in different cells of the nervous system. Hence, the role of GPCRs are attaining more attention in the therapeutic field of Alzheimer{\textquoteright}s disease. Specific agonists/antagonists and allosteric modulators could be the potential target for therapy against GPCR-mediated Tau phosphorylation in Alzheimer{\textquoteright}s disease. (C) 2020 IBRO. Published by Elsevier Ltd. All rights reserved.</p>
},
	keywords = {Alzheimer{\textquoteright}s disease, GPCRs, microglia, Tau internalization, Tau phosphorylation, Tau propagation},
	issn = {0306-4522},
	doi = {10.1016/j.neuroscience.2020.04.019},
	author = {Chidambaram, Hariharakrishnan and Chinnathambi, Subashchandrabose}
}
@article {48363,
	title = {Graphical Biology Insights into the dynamic interactions at chemokine-receptor interfaces and mechanistic models of chemokine binding},
	journal = {Journal of Structural Biology},
	volume = {214},
	year = {2022},
	month = {SEP},
	pages = {107877},
	type = {Article},
	abstract = {<p>
	Chemokine receptors are the central signaling hubs of several processes such as cell migration, chemotaxis and cell positioning. In this graphical review, we provide an overview of the structural and mechanistic principles governing chemokine recognition that are currently emerging. Structural models of chemokine-receptor cocomplexes with endogenous chemokines, viral chemokines and therapeutics have been resolved that highlight multiple interaction sites, termed as CRS1, CRS1.5 etc. The first site of interaction has been shown to be the Nterminal domain of the receptors (CRS1 site). A large structural flexibility of the N-terminal domain has been reported that was supported by both experimental and simulation studies. Upon chemokine binding, the Nterminal domain appears to show constricted dynamics and opens up to interact with the chemokine via a large interface. The subsequent sites such as CRS1.5 and CRS2 sites have been structurally well resolved although differences arise such as the localization of the N-terminus of the ligand to a major or minor pocket of the orthosteric binding site. Several computational studies have highlighted the dynamic protein-protein interface at the CRS1 site that seemingly appears to resolve the differences in NMR and mutagenesis studies. Interestingly, the differential dynamics at the CRS1 site suggests a mixed model of binding with complex signatures of both conformational selection and induced fit models. Integrative experimental and computational approaches could help unravel the structural basis of promiscuity and specificity in chemokine-receptor binding and open up new avenues of therapeutic design.</p>
},
	keywords = {Chemokine receptors, GPCRs, Intrinsically disordered protein domains, protein-protein interactions},
	issn = {1047-8477},
	doi = {10.1016/j.jsb.2022.107877},
	author = {Sonawani, Archana and Kharche, Shalmali and Dasgupta, Debjani and Sengupta, Durba}
}
