1J8I

Solution Structure of Human Lymphotactin

Summary for 1J8I

• Entry DOI: 10.2210/pdb1j8i/pdb
• NMR Information: BMRB: 5042
• Descriptor: Lymphotactin (1 entity in total)
• Functional Keywords: chemokine, cytokine
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P47992
• Total number of polymer chains: 1
• Total formula weight: 10286.79

Authors

Kuloglu, E.S.,McCaslin, D.R.,Markley, J.L.,Pauza, C.D.,Volkman, B.F. (deposition date: 2001-05-21, release date: 2001-10-24, Last modification date: 2024-11-20)

Primary citation

Kuloglu, E.S.,McCaslin, D.R.,Kitabwalla, M.,Pauza, C.D.,Markley, J.L.,Volkman, B.F.
Monomeric solution structure of the prototypical 'C' chemokine lymphotactin.
Biochemistry, 40:12486-12496, 2001

PubMed Abstract: Lymphotactin, the sole identified member of the C class of chemokines, specifically attracts T lymphocytes and natural killer cells. This 93-residue protein lacks 2 of the 4 conserved cysteine residues characteristic of the other 3 classes of chemokines and possesses an extended carboxyl terminus, which is required for chemotactic activity. We have determined the three-dimensional solution structure of recombinant human lymphotactin by NMR spectroscopy. Under the conditions used for the structure determination, lymphotactin was predominantly monomeric; however, pulsed field gradient NMR self-diffusion measurements and analytical ultracentrifugation revealed evidence of dimer formation. Sequence-specific chemical shift assignments were determined through analysis of two- and three-dimensional NMR spectra of (15)N- and (13)C/(15)N-enriched protein samples. Input for the torsion angle dynamics calculations used in determining the structure included 1258 unique NOE-derived distance constraints and 60 dihedral angle constraints obtained from chemical-shift-based searching of a protein conformational database. The ensemble of 20 structures chosen to represent the structure had backbone and heavy atom rms deviations of 0.46 +/- 0.11 and 1.02 +/- 0.14 A, respectively. The results revealed that human lymphotactin adopts the conserved chemokine fold, which is characterized by a three-stranded antiparallel beta-sheet and a C-terminal alpha-helix. Two regions are dynamically disordered as evidenced by (1)H and (13)C chemical shifts and [(15)N]-(1)H NOEs: residues 1-9 of the amino terminus and residues 69-93 of the C-terminal extension. A functional role for the C-terminal extension, which is unique to lymphotactin, remains to be elucidated.

PubMed: 11601972
DOI: 10.1021/bi011106p

Experimental method

SOLUTION NMR