2JP1

Solution structure of the alternative conformation of XCL1/Lymphotactin

2JP1 の概要

• エントリーDOI: 10.2210/pdb2jp1/pdb
• NMR情報: BMRB: 15215
• 分子名称: Lymphotactin (1 entity in total)
• 機能のキーワード: lymphotactin, xcl1, chemokine, structural rearrangement, protein folding, cytokine
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P47992
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 20573.58

構造登録者

Volkman, B.F.,Tuinstra, R.L.,Peterson, F.C. (登録日: 2007-04-17, 公開日: 2008-03-11, 最終更新日: 2024-11-20)

主引用文献

Tuinstra, R.L.,Peterson, F.C.,Kutlesa, S.,Elgin, E.S.,Kron, M.A.,Volkman, B.F.
Interconversion between two unrelated protein folds in the lymphotactin native state
Proc.Natl.Acad.Sci.Usa, 105:5057-5062, 2008

PubMed 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 beta-sheet and carboxyl-terminal helix. The second Ltn structure solved by NMR reveals a dimeric all-beta-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.

PubMed: 18364395
DOI: 10.1073/pnas.0709518105

実験手法

SOLUTION NMR