Interconversion between two unrelated protein folds in the lymphotactin native state

@article{citeulike:2622751, abstract = {Proteins often have multiple functional states, which might not always be accommodated by a single fold. Lymphotactin (Ltn) adopts two distinct structures in equilibrium, one corresponding to the canonical chemokine fold consisting of a monomeric three-stranded -sheet and carboxyl-terminal helix. The second Ltn structure solved by NMR reveals a dimeric all--sheet arrangement with no similarity to other known proteins. In physiological solution conditions, both structures are significantly populated and interconvert rapidly. Interconversion replaces long-range interactions that stabilize the chemokine fold with an entirely new set of tertiary and quaternary contacts. The chemokine-like Ltn conformation is a functional XCR1 agonist, but fails to bind heparin. In contrast, the alternative structure binds glycosaminoglycans with high affinity but fails to activate XCR1. Because each structural species displays only one of the two functional properties essential for activity in vivo, the conformational equilibrium is likely to be essential for the biological activity of lymphotactin. These results demonstrate that the functional repertoire and regulation of a single naturally occurring amino acid sequence can be expanded by access to a set of highly dissimilar native-state structures. 10.1073/pnas.0709518105}, author = {Tuinstra, Robbyn L. and Peterson, Francis C. and Kutlesa, Snjezana and Elgin, Sonay E. and Kron, Michael A. and Volkman, Brian F. }, citeulike-article-id = {2622751}, doi = {http://dx.doi.org/10.1073/pnas.0709518105}, journal = {Proceedings of the National Academy of Sciences}, keywords = {dimerization, experiment, nmr, structural\_change}, month = {April}, number = {13}, pages = {5057--5062}, posted-at = {2008-04-02 10:10:53}, priority = {2}, title = {Interconversion between two unrelated protein folds in the lymphotactin native state}, url = {http://dx.doi.org/10.1073/pnas.0709518105}, volume = {105}, year = {2008} }

TY - JOUR ID - citeulike:2622751 L3 - citeulike-article-id:2622751 TI - Interconversion between two unrelated protein folds in the lymphotactin native state JF - Proceedings of the National Academy of Sciences VL - 105 IS - 13 SP - 5057 EP - 5062 N2 - Proteins often have multiple functional states, which might not always be accommodated by a single fold. Lymphotactin (Ltn) adopts two distinct structures in equilibrium, one corresponding to the canonical chemokine fold consisting of a monomeric three-stranded -sheet and carboxyl-terminal helix. The second Ltn structure solved by NMR reveals a dimeric all--sheet arrangement with no similarity to other known proteins. In physiological solution conditions, both structures are significantly populated and interconvert rapidly. Interconversion replaces long-range interactions that stabilize the chemokine fold with an entirely new set of tertiary and quaternary contacts. The chemokine-like Ltn conformation is a functional XCR1 agonist, but fails to bind heparin. In contrast, the alternative structure binds glycosaminoglycans with high affinity but fails to activate XCR1. Because each structural species displays only one of the two functional properties essential for activity in vivo, the conformational equilibrium is likely to be essential for the biological activity of lymphotactin. These results demonstrate that the functional repertoire and regulation of a single naturally occurring amino acid sequence can be expanded by access to a set of highly dissimilar native-state structures. 10.1073/pnas.0709518105 KW - dimerization KW - experiment KW - nmr KW - structural_change AU - Tuinstra, Robbyn AU - Peterson, Francis AU - Kutlesa, Snjezana AU - Elgin, Sonay AU - Kron, Michael AU - Volkman, Brian PY - 2008/04/01/ UR - http://dx.doi.org/10.1073/pnas.0709518105 ER -