bi026020q_si_001.pdf (52.4 kB)
The CXCR3 Binding Chemokine IP-10/CXCL10: Structure and Receptor Interactions†
journal contribution
posted on 2002-07-23, 00:00 authored by Valerie Booth, David W. Keizer, Monique B. Kamphuis, Ian Clark-Lewis, Brian D. SykesThe structure of IP-10 was solved by NMR spectroscopy and represents the first structure
from the class of agonists toward the receptor CXCR3. CXCR3 binding chemokines are unique in their
ability to bind receptors from both the CC and CXC classes of chemokine receptors. An unusual structural
feature of IP-10 was identified that may provide the basis for the ability of IP-10 to bind both CXCR3
and CCR3. The surface of IP-10 that interacts with the N-terminus of CXCR3 was defined by monitoring
changes in the NMR spectrum of IP-10 upon addition of a CXCR3 N-terminal peptide. These studies
indicated that the interaction involves a hydrophobic cleft, formed by the N-loop and 40s-loop region of
IP-10, similar to the interaction surface observed for other chemokines such as IL-8. An additional region
of interaction was observed that consists of a hydrophobic cleft formed by the N-terminus of IP-10 and
30s-loop of IP-10.