1b2t
SOLUTION STRUCTURE OF THE CX3C CHEMOKINE DOMAIN OF FRACTALKINE
Structural highlights
FunctionX3CL1_HUMAN The soluble form is chemotactic for T-cells and monocytes, but not for neutrophils. The membrane-bound form promotes adhesion of those leukocytes to endothelial cells. May play a role in regulating leukocyte adhesion and migration processes at the endothelium. Binds to CX3CR1.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedFractalkine, a novel CX3C chemokine, is unusual because of both its membrane-associated structure and its direct role in cell adhesion. We have solved the solution structure of the chemokine domain of fractalkine (residues 1-76) by heteronuclear NMR methods. The 20 lowest energy structures in the ensemble have an average backbone rmsd of 0.43 A, excluding the termini. In contrast to many other chemokines which form homodimers, fractalkine's chemokine module is monomeric. Comparison of the structure to CC and CXC chemokines reveals interesting differences which are likely to be relevant to receptor binding. These include a bulge formed by the CX3C motif, the relative orientation of the N-terminus and 30's loop (residues 30-38), and the conformation of the N-loop (residues 9-19). 15N backbone relaxation experiments indicate that these same regions of the protein are dynamic. We also titrated 15N-labeled protein with a peptide from the N-terminus of the receptor CX3CR1 and confirmed that this region of the receptor contacts the fractalkine chemokine domain. Interestingly, the binding site maps roughly to the regions of greatest flexibility and structural variability. Together, these data provide a first glimpse of how fractalkine interacts with its receptor and should help guide mutagenesis studies to further elucidate the molecular details of binding and signaling through CX3CR1. Solution structure and dynamics of the CX3C chemokine domain of fractalkine and its interaction with an N-terminal fragment of CX3CR1.,Mizoue LS, Bazan JF, Johnson EC, Handel TM Biochemistry. 1999 Feb 2;38(5):1402-14. PMID:9931005[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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