Crystal structures of oligomeric forms of the IP-10/CXCL10 chemokine.
We have determined the structure of wild-type IP-10 from three crystal forms. The crystals provide eight separate models of the IP-10 chain, all differing substantially from a monomeric IP-10 variant examined previously by NMR spectroscopy. In each crystal form, IP-10 chains form conventional beta sheet dimers, which, in turn, form a distinct tetrameric assembly. The M form tetramer is reminiscent of platelet factor 4, whereas the T and H forms feature a novel twelve-stranded beta sheet. Analytical ultracentrifugation indicates that, in free solution, IP-10 exists in a monomer-dimer equilibrium with a dissociation constant of 9 microM. We propose that the tetrameric structures may represent species promoted by the binding of glycosaminoglycans. The binding sites for several IP-10-neutralizing mAbs have also been mapped.
Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom.
G Jawahar
GJ
Swaminathan
Daniel E
DE
Holloway
Richard A
RA
Colvin
Gabriele K
GK
Campanella
Anastassios C
AC
Papageorgiou
Andrew D
AD
Luster
K Ravi
KR
Acharya
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D014461:Ultracentrifugation
C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine