biostudies-literatureDishman AFNIAID NIH HHSNCI NIH HHSNational Institutes of HealthNIH HHSNIGMS NIH HHSe23402https://www.ebi.ac.uk/biostudies/studies/S-EPMC8004533biostudies-literatureUnknown112(10)The metamorphic protein XCL1 switches between two distinct native structures with different functions in the human immune system. This structural interconversion requires complete rearrangement of all hydrogen bonding networks, yet fold-switching occurs spontaneously and reversibly in solution. One structure occupies the canonical α-β chemokine fold and binds XCL1's cognate G-protein coupled receptor, while the other structure occupies a dimeric, all-β fold that binds glycosaminoglycans and has antimicrobial activity. Both of these functions are important for the biologic role of XCL1 in the immune system, and each structure is approximately equally populated under near-physiologic conditions. Recent work has begun to illuminate XCL1's role in combatting infection and cancer. However, withBiopolymersSpecific binding-induced modulation of the XCL1 metamorphic equilibrium.PMC8004533F30 CA236182S10 OD020000R37 AI058072R01 AI058072T32 GM080202S10 OD025000Dishman AFVolkman BFPeterson FCfalseSpecific binding-induced modulation of the XCL1 metamorphic equilibrium.The metamorphic protein XCL1 switches between two distinct native structures with different functions in the human immune system. This structural interconversion requires complete rearrangement of all hydrogen bonding networks, yet fold-switching occurs spontaneously and reversibly in solution. One structure occupies the canonical α-β chemokine fold and binds XCL1's cognate G-protein coupled receptor, while the other structure occupies a dimeric, all-β fold that binds glycosaminoglycans and has antimicrobial activity. Both of these functions are important for the biologic role of XCL1 in the immune system, and each structure is approximately equally populated under near-physiologic conditions. Recent work has begun to illuminate XCL1's role in combatting infection and cancer. However, with2021-01-01T00:00:00Z2021 Oct2025-04-21T23:42:31.199Z2025-04-05T19:13:13.702ZS-EPMC80045333298685810.1002/bip.23402