Engineering Metamorphic Chemokine Lymphotactin/XCL1 into the GAG-Binding, HIV-Inhibitory Dimer Conformation.

ABSTRACT: Unlike other chemokines, XCL1 undergoes a distinct metamorphic interconversion between a canonical monomeric chemokine fold and a unique β-sandwich dimer. The monomeric conformation binds and activates the receptor XCR1, whereas the dimer binds extracellular matrix glycosaminoglycans and has been associated with anti-human immunodeficiency virus (HIV) activity. Functional studies of WT-XCL1 are complex, as both conformations are populated in solution. To overcome this limitation, we engineered a stabilized dimeric variant of XCL1 designated CC5. This variant features a new disulfide bond (A36C-A49C) that prevents structural interconversion by locking the chemokine into the β-sandwich dimeric conformation, as demonstrated by NMR structural analysis and hydrogen/deuterium exchange experiment

SUBMITTER: Fox JC 

PROVIDER: S-EPMC5028202 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature