2HDM

Solution structure of V21C/V59C Lymphotactin/XCL1

2HDM の概要

• エントリーDOI: 10.2210/pdb2hdm/pdb
• NMR情報: BMRB: 15110
• 分子名称: Lymphotactin (1 entity in total)
• 機能のキーワード: lymphotactin, xcl1, chemokine, conformational restriction, 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: 1
• 化学式量合計: 10195.68

構造登録者

Volkman, B.F.,Tuinstra, R.L.,Peterson, F.C.,Elgin, E.S. (登録日: 2006-06-20, 公開日: 2007-05-01, 最終更新日: 2024-10-09)

主引用文献

Tuinstra, R.L.,Peterson, F.C.,Elgin, E.S.,Pelzek, A.J.,Volkman, B.F.
An engineered second disulfide bond restricts lymphotactin/XCL1 to a chemokine-like conformation with XCR1 agonist activity
Biochemistry, 46:2564-2573, 2007

PubMed Abstract: Chemokines adopt a conserved tertiary structure stabilized by two disulfide bridges and direct the migration of leukocytes. Lymphotactin (Ltn) is a unique chemokine in that it contains only one disulfide and exhibits large-scale structural heterogeneity. Under physiological solution conditions (37 degrees C and 150 mM NaCl), Ltn is in equilibrium between the canonical chemokine fold (Ltn10) and a distinct four-stranded beta-sheet (Ltn40). Consequently, it has not been possible to address the biological significance of each structural species independently. To stabilize the Ltn10 structure in a manner independent of specific solution conditions, Ltn variants containing a second disulfide bridge were designed. Placement of the new cysteines was based on a sequence alignment of Ltn with either the first (Ltn-CC1) or third disulfide (Ltn-CC3) in the CC chemokine, HCC-2. NMR data demonstrate that both CC1 and CC3 retain the Ltn10 chemokine structure and no longer exhibit structural rearrangement. The ability of each mutant to activate the Ltn receptor, XCR1, has been tested using an intracellular Ca2+ flux assay. These data support the conclusion that the chemokine fold of Ltn10 is responsible for receptor activation. We also examined the role of amino- and carboxyl-terminal residues in Ltn-mediated receptor activation. In contrast to previous reports, we find that the 25 residues comprising the novel C-terminal extension do not participate in receptor activation, while the native N-terminus is absolutely required for Ltn function.

PubMed: 17302442
DOI: 10.1021/bi602365d

実験手法

SOLUTION NMR