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2HDM

Solution structure of V21C/V59C Lymphotactin/XCL1

Summary for 2HDM
Entry DOI10.2210/pdb2hdm/pdb
NMR InformationBMRB: 15110
DescriptorLymphotactin (1 entity in total)
Functional Keywordslymphotactin, xcl1, chemokine, conformational restriction, cytokine
Biological sourceHomo sapiens (human)
Cellular locationSecreted: P47992
Total number of polymer chains1
Total formula weight10195.68
Authors
Volkman, B.F.,Tuinstra, R.L.,Peterson, F.C.,Elgin, E.S. (deposition date: 2006-06-20, release date: 2007-05-01, Last modification date: 2024-10-09)
Primary citationTuinstra, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
SOLUTION NMR
Structure validation

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