Solution structure of CCL21 and identification of a putative CCR7 binding site.
CCL21 is a human chemokine that recruits normal immune cells and metastasizing tumor cells to lymph nodes through activation of the G protein-coupled receptor CCR7. The CCL21 structure solved by NMR contains a conserved chemokine domain followed by an extended, unstructured C-terminus that is not typical of most other chemokines. A sedimentation equilibrium study showed CCL21 to be monomeric. Chemical shift mapping indicates that the CCR7 N-terminus binds to the N-loop and third β-strand of CCL21's chemokine domain. Details of CCL21-receptor recognition may enable structure-based drug discovery of novel antimetastatic agents.
Department of Chemistry, University of Wisconsin-Whitewater, Whitewater, Wisconsin 53190, United States.
Melissa
M
Love
Jamie L
JL
Sandberg
Joshua J
JJ
Ziarek
Kyle P
KP
Gerarden
Renee R
RR
Rode
Davin R
DR
Jensen
Darrell R
DR
McCaslin
Francis C
FC
Peterson
Christopher T
CT
Veldkamp
D001665:Binding Sites; D054421:Chemokine CCL21 / Q000737:chemistry* / Q000378:metabolism*; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D054400:Receptors, CCR7 / Q000737:chemistry* / Q000378:metabolism*
C515370:CCR7 protein, human; D054421:Chemokine CCL21; D054400:Receptors, CCR7