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CXCR4, a member of the family of chemokine-activated G protein-coupled receptors, is widely expressed in immune response cells. It is involved in both cancer development and progression as well as viral infection, notably by HIV-1. A variety of methods, including structural information, have suggested the receptor may exist as a dimer or oligomer. However, the mechanistic details surrounding receptor oligomerization and its potential dynamic regulation remain unclear. Using both biochemical and biophysical means we confirm that CXCR4 can exist as a mixture of monomers, dimers and higher-order oligomers in cell membranes and show that oligomeric structure becomes more complex as receptor expression levels increase. Mutations of CXCR4 residues located at a putative dimerization interface result in monomerization of the receptor. Additionally, binding of the CXCR4 antagonist IT1t— a small, drug-like isothiourea derivative — rapidly destabilizes the oligomeric structure, while AMD3100, another well-characterized CXCR4 antagonist, does not. Although a mutation that regulates constitutive activity of CXCR4 also results in monomerization of the receptor, binding of IT1t to this variant promotes receptor dimerization. These results provide novel insights into the basal organization of CXCR4 and how antagonist ligands of different chemotypes differentially regulate its oligomerization state.

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This article begins to examine the history of economic and social ideas launched or nurtured by the United Nations (UN). In 1999, the United Nations Intellectual History Project was initiated, to analyse the UN as an intellectual actor, and to shed light on the role of the UN system in creating knowledge and in influencing international policy‐making: this article is based on the first five books and the oral histories from that Project. The starting point is that ideas may be the most important legacy of the UN for human rights, economic and social development, as well as for peace and security. For the authors, this ‘intellectual history’ provides a way to explore the origins of particular ideas; trace their course within institutions, scholarship, and discourse; and in some cases evaluate the impact of ideas on policy and action.